PSG are on 69 points with four games left with Monaco trailing by 11 points
The Argentine forward, who joined on a two-year contract from Barcelona during the close season, has played only half an hour as a second-half substitute in a Ligue 1 game in Reims last month.
Messi's inclusion also marked the first time he will play alongside both Brazil forward Neymar and France striker Kylian Mbappe.
In the absence of the injured Marco Verratti and the suspended Idrissa Gueye, Ander Herrera, Georginio Wijnaldum and Leandro Paredes will form the three-man midfield.
Keylor Navas will start as goalkeeper rather than new signing Gianluigi Donnarumma.