O'Driscoll partners Andrew Goodman in the centre with Ireland international Fergus McFadden named on the right wing, in a back-three which also includes Fionn Carr and Isa Nacewa.
Leinster are also boosted by the return of Jonathan Sexton from injury and he will line out in blue for the first time since the Heineken Cup victory over Exeter Chiefs in January, earning his 105th Leinster cap.
The St. Mary's College clubman lines out at half-back alongside John Cooney in a starting line up which includes three former Gonzaga College graduates.
In the pack, Kevin McLaughlin forms an abrasive back row unit with number 8 Rhys Ruddock and Dominic Ryan.
Tom Denton packs down alongside Devin Toner in the second row, while loosehead prop Jack McGrath will make his 33rd appearance in a front row which also features Richardt Strauss and Michael Bent.
Academy out-half Cathal Marsh, a regular starter for Leinster 'A', is in line to make his senior debut for the province should he feature off the bench.
Sunday's league fixture will raise money for the provinces of Emilia and Lombardia which were affected by an earthquake last year.
LEINSTER (v Zebre): Isa Nacewa; Fergus McFadden, Brian O'Driscoll (capt), Andrew Goodman, Fionn Carr; Jonathan Sexton, John Cooney; Jack McGrath, Richardt Strauss, Michael Bent, Tom Denton, Devin Toner, Kevin McLaughlin, Dominic Ryan, Rhys Ruddock.
Replacements: Aaron Dundon, Jack O'Connell, Jamie Hagan, Quinn Roux, Leo Auva'a, Isaac Boss, Cathal Marsh, Andrew Conway.