Paul O'Connell, Conor Murray and Peter O'Mahony all come into the side for a game that sees Tipperary's Tommy O'Donnell earn his 99th cap for his province.
Anthony Foley's side need a win to keep up their hopes of a semi final berth.
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Kick off at Murrayfield is at 7.30pm.
Meanwhile, Ulster have gained a valuable bonus point in their hunt for a play-off place.
Tommy Bowe got two of their five tries in a 27-20 win over Connacht at the Sportsground.
Elsewhere, it's finished Zebre 26 Scarlets 28.
