The Demons have made just one change with the 33-year-old returning for forward Addam Maric.
Maric has been relegated to an emergency after playing his first match for the season in last round’s 73-point win over the Sydney Swans.
The third-year Demon showed some good signs in just his 12th AFL match, collecting 17 disposals.
But it was always going to be a difficult match committee for the Melbourne coaching hierarchy, considering the skipper was back in the frame.
Outstanding first-year midfielder Jack Trengove, who has missed the past two matches with a hip injury, is also an emergency, along with key defender Matthew Warnock.
McDonald made a successful comeback in the VFL last Sunday, collecting 24 disposals for Casey against Collingwood at Victoria Park.
But his last appearance for the Demons was on June 5 against Carlton.
Up until that point, McDonald was among Melbourne’s best performers, rivaling his 2006/07 club champion years.
He now needs just four more appearances to become the seventh player to play 250 matches for Melbourne.
A corked thigh suffered against Fremantle in round 16 has again ruled out tough-nut ball-winner Brent Moloney.
This will be Melbourne’s first non-Sunday match since round 12 and its final Saturday for the 2010 home-and-away season.
Melbourne
HB: Cameron Bruce, James Frawley, Joel Macdonald
C: Rohan Bail, James McDonald, Brad Green
HF: Lynden Dunn, Jack Watts, Tom Scully
F: Jamie Bennell, Paul Johnson, Austin Wonaeamirri
FOLL: Mark Jamar, Colin Sylvia Aaron Davey
I/C: Jordie McKenzie, Cale Morton, Nathan Jones, Liam Jurrah
Out: Maric
Brisbane Lions
HB: Luke Power, Brent Staker, Joel Patfull
C: Jack Redden, Daniel Rich, Tom Rockliff
HF: James Polkinghorne, Jonathan Brown, Albert Proud
F: Jared Brennan, Brendan Fevola, Todd Banfield
Foll: Mitchell Clark, Simon Black, Michael Rischitelli
I/C: Pearce Hanley, Cheynee Stiller, Ryan Harwood, Matthew Leuenberger
Emg: James Hawksley, Aaron Cornelius, Justin Sherman
In: McGrath, Clarke, Stiller, Black
Out: Amon Buchanan (quad), Matt Maguire, James Hawksley, Aaron Cornelius