In all, head coach Joe Schmidt has made ten changes in personnel to the side that started last weekend's derby win over Ulster.
The back-three is completed by full-back David Kearney, who will make his 11th appearance of the season, and Luke Fitzgerald.
Eoin Reddan links up at half-back with the 22-year-old Ian Madigan, who is set for his 15th appearance of the current campaign.
In the pack, Cian Healy and Mike Ross form an all-changed front row alongside hooker Jason Harris-Wright, with Scotland international Nathan Hines joining Devin Toner in the second row.
Shane Jennings, Sean O'Brien and Rhys Ruddock make up an all-Ireland back row. O'Brien and Ruddock come in for Jamie Heaslip and Kevin McLaughlin respectively.
Shane Horgan, who scored two tries in the 34-26 victory over Ulster, is one of four Ireland internationals on the replacements bench alongside Isaac Boss, Leo Cullen and Jonathan Sexton.
It will be Ruddock's first start since last month's Magners League win over the Newport Gwent Dragons at Rodney Parade.
"There's a lot of competition for places. Kevin's playing well, Dominic's playing well, so that has to spur to me on," said the young flanker.
"I've had plenty of opportunities and I need to take them and start playing well. I think I played better earlier in the season, so I need to get back to that form and try and get the jersey.
"I had a good run of games (early in season) and then with the internationals I had quite a few games but my form sort of dipped around that period.
"I've also been feeling sick for the last few weeks so now I'm better there's no excuses. I've got the opportunity and I have to take it."
LEINSTER (v Aironi Rugby): David Kearney; Fergus McFadden, Brian O'Driscoll (capt), Eoin O'Malley, Luke Fitzgerald; Ian Madigan, Eoin Reddan; Cian Healy, Jason Harris-Wright, Mike Ross, Devin Toner, Nathan Hines, Rhys Ruddock, Shane Jennings, Sean O'Brien.
Replacements: Richardt Strauss, Heinke van der Merwe, Stan Wright, Leo Cullen, Dominic Ryan, Isaac Boss, Jonathan Sexton, Shane Horgan.