The Dutch head coach suffered his first Serie A defeat at the hands of Napoli last week and will be desperate to bounce back against a side with a poor San Siro record
The Dutchman had led his charges to Serie A victories over Hellas Verona and Cagliari and a draw against Torino before his side's league resurgence was ended by Napoli.
Adel Taarabt looked to have set the visitors on their way to what would have been an impressive victory with a debut goal but Gokhan Inler struck three minutes later before Gonzalo Higuain's second-half double condemned Milan to defeat.
It ensured Milan dropped back into the bottom half of the table and brought home the task Seedorf faces to salvage anything from their season.
Victory could move them ninth if results involving Genoa and Lazio go their way and the history books will fill Milan with confidence.
Bologna have not beaten Milan since August 2008, taking just four points from a possible 30 since then, although they came within two minutes of victory in the sides' reverse fixture in September, with late goals from Robinho and Ignazio Abate rescuing a draw for at the Stadio Renato Dall'Ara.
Davide Ballardini's men recorded their first win of the year last time out against Torino.
Jonathan Cristaldo's brace helped his side end a run of five games without a win and a further victory on Friday would move them seven points clear of the relegation zone, with those around them all playing on Sunday.
Mario Balotelli will be eager to silence critics after his emotional outburst in the defeat to Napoli, with the striker having scored four goals in his last five games, although Giampaolo Pazzini has proven a thorn in the side for Bologna historically, with five goals in his last three outings against the Rossoblu.
Midfielder Diego Laxalt registered both his league goals this season against Milan in the reverse fixture, but they will have to make do without Alessandro Diamanti following his move to Guangzhou Evergrande in China, with the Italy international having scored three times in three seasons against the Rossoneri.
Bologna forward Lazaros Christodoulopoulos is yet to find the net for the club this season but believes their win in Torino can act as a springboard as they seek to move up the table from 16th.
"The victory in Turin should be the starting point, from this performance we have to build the rest of our journey," he said.
"Milan is certainly a great team but they are not experiencing an exciting time. With care and courage behind the counterattack we have the ability to do well."