Ireland flanker Dan Leavy could make his first Leinster appearance in 19 months against Zebre in the Pro14 on Friday.
Leavy injured his knee in a Champions Cup quarter-final against Ulster in March 2019 and has been named on the bench for the game at the RDS.
Devin Toner wins his 250th Leinster cap while Dave Kearney returns from injury to make his 150th appearance.
Hooker Dan Sheehan and centre Liam Turner will make their senior debuts.
Prop Ciaran Parker and centre David Hawkshaw could also make their maiden appearances from the bench.
Leo Cullen is without a number of Ireland internationals, including Will Connors and Hugo Keenan, both of whom are set to make their international debuts against Italy.
Pro14 holders Leinster top Conference A after two wins from their opening two games, in contrast to Zebre who are yet to pick up a point.
Debutant Sheehan starts at hooker either side of Michael Bent and Peter Dooley, while Ross Molony and Devin Toner provide plenty of experience at lock with nearly 350 Leinster caps between them.
The back row is made up of Josh Murphy, Scott Penny and captain Rhys Ruddock, with the returning Leavy providing cover on the bench.
Luke McGrath and Harry Byrne start at half-back while Ciaran Frawley is joined in the centre by Ireland Under-20s Grand Slam winning centre Turner.
The back three are making their first starts of the season, with Jimmy O'Brien and Tommy O'Brien impressing off the bench away to Benetton Rugby while Dave Kearney returns after a hamstring injury.
Zebre have made 13 changes to the side beaten at Dragons, with wings Pierre Bruno and Jamie Elliott among eight players making their first starts of the season.
Ex-Leinstermen Mick Kearney and Ian Nagle start for the visitors, who are captained by centre Tommaso Boni.
Leinster: J O'Brien, T O'Brien; Turner, Frawley; Kearney; H Byrne, McGrath; Bent, Sheehan, Dooley; Molony, Toner; Murphy, Penny, Ruddock.
Replacements: Tracy, Milne, Parker, Dunne, Fardy, O'Sullivan, Hawkshaw, Leavy.
Zebre: Biondelli, Bruno; Boni, Lucchin; Elliott; Pescetto, Casilio; Buonfiglio, Manfredi, Tarus; Kearney, Nagle; Masselli, Giammarioli, Tuivaiti.
Replacements: Fabiani, Lovotti, Nocera, Krumov, Ortis, Renton, Rizzi, Laloifi.