MacDonald had little hesitation in naming former Leeds United
midfielder Milner in the squad for the first game of the season after a delay in his anticipated move to Manchester City.
MacDonald is also confident Milner's fitness levels will not be an issue even though he has played only 23 minutes – for England against Hungary on Wednesday – since the World Cup.
Former Liverpool midfielder MacDonald said: "I didn't have to think hard about putting James in the squad. It was a pretty straightforward decision for me. You need to get your best players on the pitch. James is one of our best players.
"James would also have the mental strength to deal with it if the crowd reaction is hostile. He is a tough lad.
"I would expect him not to let it affect him and he is very much a team player."
MacDonald is hoping the Villa fans will react positively to the former Newcastle player.
He said: "I hope the fans don't get on his back.
"I hope they get behind him and say 'whatever happens, he is playing for us today' and look what he has done for us over the previous couple of years."
Milner was left out of Villa's pre-season games after reporting back for duty a month after being involved in South Africa.
But MacDonald said: "James is one of the fittest players I've come across in my life – and I've come across some very, very fit ones.
"The amount of work and running he has done in training would tell me he would have no problems if he was selected to start."
MacDonald would also like Milner to remain at Villa long term, although at this juncture it still seems likely a move to Eastlands will eventually go through.
He said: "I would love James Milner to be playing for Villa for a few years. I think he is a very talented player, obviously very sought-after by clubs.
"He would only make our team better if he was to stay."
Manchester City manager Roberto Mancini last night remained confident about his chances of getting Milner.
City are believed to be offering a player-plus-cash deal involving Stephen Ireland to meet Villa's 30m valuation.
The hold-up is believed to be that Ireland is reportedly demanding 2m in compensation to go the other way.
However, Mancini did have a signing to celebrate last night after City completed the capture of Italy striker Mario Balotelli from Inter Milan.
The Eastlands outfit have been pursuing Balotelli for much of the summer and finally landed him on a five-year deal after agreeing an undisclosed fee with Inter thought to be around 22m.
But the new Italy international will be available for the home
encounter with Liverpool on August 23.
He can play in a variety of forward positions and will compete for a place with Carlos Tevez, Emmanuel Adebayor and Roque Santa Cruz in Mancini's vast squad.
Although Balotelli has been involved in plenty of controversial incidents in the past, Mancini has not been put off signing a player he knows well from his days at Inter Milan.
And he is convinced the player's muscular style is perfectly suited to the English game.
"Mario is one of the best players of his age in Europe, and I'm very happy to be working with him again," Mancini said.
"His style of play will suit the Premier League, and because he is still so young there is a big chance for him to improve. He is a strong and exciting player, and City fans will enjoy him."
He follows Jerome Boateng, Yaya Toure, Aleksander Kolarov and David Silva into Eastlands and is one of the major reasons why Mancini will be content to discard Craig Bellamy.
Mancini yesterday accused Bellamy of making false statements about him. Bellamy has been hit by a massive fine after claiming the Italian was trying to force him out of Eastlands. He also alleged Mancini had stopped speaking to him, widening the rift still further.