In the first leg at Old Trafford which ended 1-1, Rashford was was out due to injury and the Red Devils missed him terribly, with his pace and direct running absent which allowed Milan to take a foothold over proceedings.
However, he returned to action in the Premier League at the weekend as Man Utd were uninspiring in a 1-0 win against West Ham, so he will likely feature from the starting XI versus the Serie A giants for European action.
Man Utd have a few other injury boosts that will see them travel to Italy with a much stronger squad that featured in the first leg.
Paul Pogba and Edinson Cavani missed that game during a period away, but both returned to full training this week and could play a part, though it remains to be seen if it will be from the opening whistle.
Ole Gunnar Solskjaer was without Anthony Martial for the West Ham game, but he is expected to be fit, too.
Donny van de Beek also returned to training, but it is unlikely he would have featured in the starting XI in the second leg anyway.
David de Gea is back with his team-mates following the birth of his child, but Dean Henderson will likely be given the nod again for the moment.
Aaron Wan-Bissaka, Eric Bailly, and Harry Maguire will start at the back, while Luke Shaw could be preferred to Alex Telles at left-back.
As the game is away from home Solskjaer will probably go for Scott McTominay and Fred in the middle midfield again, with Paul Pogba perhaps playing in an inverted role down the right wing, as he has done a few times this campaign.
Bruno Fernandes is a sure-fire starter, and if fit Rashford will start on the left with Cavani leading the line.