Beckham is far from certain to start after an unconvincing display in central midfield at the San Siro that saw the 34 year-old substituted mid-way through the second half.
But the former England captain, who is on loan from MLS side LA Galaxy, is highly likely to play some role in the game and can expect a warm reception from the Old Trafford crowd.
Beckham spent his formative years with Manchester United's youth team and played alongside Gary Neville, Nicky Butt and Paul Scholes when they won the FA Youth Cup in 1992.
That famous side went on to provide the homegrown core of the squad whose domination of English football reached its peak in 1999 when United won a league, cup and Champions League treble.
"I'm not nervous," Beckham insisted in an interview with Milan's in-house television channel. "I'm happy because for the first time after seven years I will return to Manchester and go on the pitch. I'll meet up with many friends and all the people who supported me for many years.
"If I play, I won't be frightened. I'll be excited. I played in that stadium for many years and I know what it means to be a Manchester United player. I know what it means for opponents to play there.
"Playing at Old Trafford is always difficult. It's difficult to win, especially 2-0. We know we'll have to go for it. We are aware of the fact that it will be a very difficult match, but nothing's impossible."
Beckham's enduring popularity with Manchester United fans was underlined when dozens of them turned out to greet him on his arrival at Manchester airport on Tuesday, along with the inevitable scrum of photographers and reporters.
His peripheral contribution in the first leg prompted his old boss, Sir Alex Ferguson, to question the tactical judgement of his Milanese counterpart, Leonardo. On the eve of the second leg, the Scot reiterated his view that Beckham is better deployed wide on the right.
"I think David's strength has always been his crossing, and set pieces of course," Ferguson said. "That does not change, it's been his strength all his career.
"Will he play tomorrow? You tell me. I am finding it very hard to pick their team at the moment. There are lot of threats in their team of course but we are well aware of David's."
Beckham and Ferguson's relationship famously became strained in the run-up to the player's departure, with one of the manager's dressing room rants leaving the midfielder needing stitches for a wound inflicted, just above his eye, by a flying boot.
Beckham did not last long at Old Trafford after that, Ferguson having tired of the celebrity circus that had come to surround a player who scored 85 goals in 394 matches for him, winning six Premier League titles and the 1999 Champions League in the process.
The acrimony of that time now appears to have dissipated and Ferguson has recently endorsed his former player's claim to be part of England's World Cup squad in South Africa later this year, by which time he will have passed his 35th birthday.
Beckham, for his part, has always acknowledged Ferguson's central role in his development as both player and person.
"He protected his players, but he made me understand when I was making a mistake," he recalled.