Di Matteo's much-changed side created plenty of chances at Stamford Bridge but made victory harder than it should have been by failing to kill off the already-relegated Rovers
The west Londoners flew out of the blocks at Stamford Bridge, and took the lead through John Terry after half an hour, with Meireles doubling their advantage after a matter of minutes.
Blackburn pulled a goal back through Scott Dann's header, but despite the setback the home side managed to see out the win with ease.
Di Matteo made a number of changes for their final Premier League game of the season, with the Champions League final against Bayern Munich no doubt in mind.
Romelu Lukaku was handed his first league start and a chance to prove his worth up front, with Fernando Torres and Didier Drogba both rested. Ross Turnbull and Sam Hutchinson both also made the starting line-up. European suspensions meant Terry, Ramires and Branislav Ivanovic were all involved.
Heading into the game, Blackburn's fate had already been decided and therefore Steve Kean also opted to switch things around. Adam Henley, Marcus Olsson and Mauro Formica all came into the side, with reserve goalkeeper Jake Kean brought in for the injured Paul Robinson.
With just a couple of minutes on the clock the hosts nearly found a breakthrough, however Florent Malouda's cross was scrambled away by Kean.
The exciting start continued as Blackburn then had a good chance, Jason Lowe's strike from outside the box taking a wicked deflection off Raul Meireles which forced Turnbull to athletically tip it over.
Di Matteo's men hit back with two more decent attacks within the opening 15 minutes. Daniel Sturridge won a corner from Olsson, and Lukaku got himself into a good position but headed wide.
Moments later, the Belgian forward then had another chance following a neat through ball from Ramires, but Kean rushed out and timed his dive at the striker's feet perfectly.
Kean's goal continued to be threatened as Sturridge fired another low ball into the six-yard box, but the Rovers' keeper made an important interception to stop the ball from finding a Blue shirt.
The two Chelsea frontmen then linked up once more with Lukaku this time turning provider. He produced a deep cross from the right hand side, finding Sturridge at the back post. The Englishman found a yard of space but headed harmlessly wide.
Lukaku looked determined to give Di Matteo something to think about, and the Belgian was indeed the man who created the opening goal on the half-hour mark. Terry met the forward's cross from the right flank with a powerful header, which Kean could do nothing to stop.
The floodgates then looked as if they might open, as the Blues wasted no time in doubling their lead. The Blackburn defence allowed Michael Essien too much space on the edge of their box, before the Ghanaian managed to shift the ball on to Meireles who found the back of the net with a low strike.
The already-relegated side certainly seemed lacking in motivation, but the same can not be said for the Blues, as the onslaught on the visitors' goal continued.
Crosses from Lukaku and Malouda were both just about scrambled away, before the former, who looked full of confidence, played in Ramires. The Brazilian received the ball in a good position inside the Rovers' box but delayed his shot for too long and was crowded out by defenders, Chelsea entering the half-time break two goals ahead.
Two minutes into the second period and Blackburn were under pressure once more. Firstly, Sturridge skilfully cut inside onto his right foot and narrowly smashed an effort over the bar. Then, Lukaku advanced on the right flank before beating his man, only to drag a poor effort well wide.
Josh Morris replaced Formica early on in the second half, and the Blackburn player almost immediately had a golden opportunity to pull one back. However his shot was tame and Turnbull collected it with ease.
Di Matteo made a switch of their own as the hour mark approached, Didier Drogba coming on in place of the extremely lively Lukaku, both receiving standing ovations from the Blues' fans at Stamford Bridge.
The game had quietened down after that, but then out of nowhere Dann rose above Blues' goalscorer Terry to head home from a corner himself, making it 2-1.
Chelsea nearly provided an instant reply though. Kean rashly rushed out to try and meet a cross, but a mix-up with this defence led to the ball rolling to Ramires, who hit the bar with a fantastic improvised first-time effort from outside the box.
Rovers started to look as if they could get something out of the game, which became fairly stretched at times. Junior Hoilett beat a number of Blue shirts before firing over, then Drogba embarked on a powerful run, only to be denied a shot on goal by a last ditch tackle by Dann.
Both sides continued to look for the important next goal, and Sturridge came close to finding with just over 20 minutes left. The forward's strike was spectacularly saved by a diving Kean, though.
Di Matteo's men continued to dominate, but Sturridge wasted another great chance five minutes later, firing a decent opportunity wayward.
The final ten minutes saw the hosts have a few more half-chances, the likes of Torres and Sturridge attempted to penetrate the Blackburn area with no luck.
Then, in the final stages, both sides had chances to grab a late goal.
Turnbull, however, threw himself at Olsson's cross to deny Rovers and Terry failed to get a proper connection on Drogba's delivery, and Chelsea saw out a comfortable final day victory.