Messi was absent due to a fractured arm that will keep him out for three weeks but Rafinha justified being brought into the team by opening the scoring in the first half at Camp Nou on Wednesday.
Luis Suarez sent in a brilliant cross and Rafinha slotted home against his old colleagues, with Inter goalkeeper Samir Handanovic in fine form before being beaten late on by Jordi Alba.
Clement Lenglet scored an own goal against former club Sevilla last time out but he almost found the net at the right end, his header brilliantly blocked by Handanovic's legs.
Rafinha, making his fifth appearance of the season, wasted a clear sight of goal but he beat Handanovic with his next chance in the 32nd minute.
The right-wing cross from Suarez was begging to be tucked away and Rafinha, who spent time on loan at Inter last season, provided a simple first-time finish.
Matteo Politano missed a great chance to equalise in the 52nd minute when found by Mauro Icardi's cute backheel, but he blazed his shot over the crossbar.
Suarez was proving a thorn in Inter's side and, when he wriggled through on goal, Handanovic had to make a smart block to keep it 1-0, the goalkeeper then denying Lenglet again.
Philippe Coutinho almost extended Barca's lead but thudded a shot against the crossbar before Alba made certain of the points with a powerful finish after being sent through by Ivan Rakitic.
And a watching Messi was able to relax in the Camp Nou stands, his team-mates getting the job done without him.
What does it mean? No Messi, no problem ahead of Clasico
It would be inaccurate to say Barca did not miss Messi, with their attacking play lacking their usual fluency. But, as Ernesto Valverde said he hoped for in a pre-match news conference, others stepped up to address Messi's absence, a good sign with El Clasico only four days away. Barca are almost certain to top Group B, but Inter are very likely to qualify alongside them.
Suarez shines in Messi absence
Suarez stepped up to take extra responsibility with captain Messi watching on. The striker has not had the best start to the season, scoring only once in the last month, but he caused Inter problems with his relentless running, while the cross for Rafinha's opener was a peach.
Valero antics do not convince
The game was mostly played in the right spirit with both teams clearly respectful of each other. But Borja Valero's attempt to get Gerard Pique sent off was rightly ignored by referee Ovidiu Hategan. Pique caught Valero on the ear but the Inter midfielder crashed to the ground like he had been clobbered by Anthony Joshua.
Key Opta Facts
- Rafinha scored his first goal in the Champions League after 18 appearances.
- Barcelona have won their first three games of a Champions League group round in each of the last three seasons.
- Barca have won 21 of their 27 Champions League games without Lionel Messi since his debut in the competition (D2 L4).
- Alba has been directly involved in more goals than any other defender in the Champions League this season (one goal and three assists).
- Barcelona have won four of their seven Champions League matches against Inter (D2 L1), with the only defeat coming in the first leg of the semi-final in 2009-10 (1-3).
- They have won 26 of their last 28 home Champions League games (D2) since losing 3-0 to Bayern Munich in May 2013, scoring 87 goals and conceding just 13 in those games.
Messi will still be out but it's a huge game for Barca next as they host Real Madrid in the first Clasico of the season on Sunday. The following day sees Inter in Serie A action away to Lazio. As for the Champions League, the two sides meet in the return fixture at San Siro on November 6.