Zlatan Ibrahimovic, Brahim Diaz, Sandro Tonali and Diogo Dalot start as Milan begin their Europa League group phase away to Diego Laxalt’s Celtic.
It kicks off at Celtic Park at 20.00 UK time (19.00 GMT).
Stefano Pioli’s men had to play three preliminary rounds to reach this phase of the competition, including a dramatic penalty shoot-out with Rio Ave.
Ibrahimovic inevitably leads the way, having scored five goals in his three competitive appearances so far this season, including a brace in Saturday’s Milan Derby win over rivals Inter.
However, Hakan Calhanoglu is ruled out for circa 10 days by a sprained ankle.
That gives Brahim Diaz an opportunity to start with Samu Castillejo and Rade Krunic, while Tonali partners Franck Kessie in midfield.
Diogo Dalot, on loan from Manchester United, makes his debut at right-back.
Celtic had been in the Champions League preliminary rounds, but were eliminated and dropped into the Europa League instead.
They have several familiar faces, including former Milan left-back Diego Laxalt and ex-Udinese midfielder Olivier Ntcham.
The Scots are missing Christopher Jullien, Hatem Abd Elhamed, Nir Bitton, James Forrest and Mikey Johnson.
Ryan Christie returns after quarantine, but recent Milan transfer target Odsonne Edouard is still waiting for his final blood tests.
These clubs have already met 10 times in their history, but all those were in the Champions League. Milan won six, drew three and lost only once, 2-1 in 2007.
The Rossoneri won the three most recent encounters without conceding a goal.
Celtic: Barkas; Duffy, Welsh, Ajer; Frimpong, Brown, McGregor, Ntcham, Laxalt; Ajeti; Griffiths
Milan: G Donnarumma; Dalot, Kjaer, Romagnoli, Theo Hernandez; Tonali, Kessie; Castillejo, Brahim Diaz, Krunic; Ibrahimovic
Ref: Jug (SVN)