Milan had an awful start to the season and, lying 15th in the Series A after eight matches, seemed to be heading for a relegation fight rather than a title battle.
However, Milan has since climbed to third _ although it is still 11 points behind leader Juventus.
Barcelona poses Milan's sternest test yet. It commands a healthy double-digit lead in the Spanish league and is well on course to recover the domestic title. That means it can devote all its attention to Europe's top competition as it searches for its fourth title in eight years.
Even though the sides will meet for the fifth time in two seasons, it will be special for Milan striker Bojan Krkic, who progressed through the ranks at Barcelona, scoring 41 goals in 163 appearances.
"It is a different game, a special game for me but I don't want to think too much about what feelings I have inside. I just want to concentrate on the game and on the 90 minutes of football that awaits us,'' Bojan said.
"I have never played against Barcelona and for that very reason this is more than just a game for me, but I'm just thinking of helping the team. It's the only thing I want to do.''
Milan will be underdogs against a Barcelona side which has lost only twice all season in the league and in Europe.
It will be the fifth time the two teams meet in the Champions League at San Siro and Milan has only won one of those encounters, in the group stage in the 2004-05 season.
"We are going through a positive period. We have to believe in ourselves,'' Bojan said.
"We have to try and work hard and go into the match knowing that we are playing in the knockout stages of the Champions League, against Barcelona, in one of the biggest matches in the world.
"This isn't a three-point match, this is a game over 180 minutes where goals are all-important. It's fundamental to score but also not to concede. We have to remain focused for the entire 180 minutes.''
Milan is still waiting on the fitness of top scorer Stephan El Shaarawy, who has been the club's most prolific and active player this season with more than 2,000 minutes of game time yielding 17 goals.
El Shaarawy came off in the draw against Cagliari with a knee injury but is back in training and Milan is hopeful the 20-year-old Italian will be fit to start.
Mario Balotelli, who has netted four goals in three matches since his tumultuous Manchester City career ended last month, will not be eligible to play because he has already represented his former club in the competition.
Barcelona will have Lionel Messi, however.
"He is a key player for the team, because of what he brings and has to offer, goals, because he is decisive,'' Barcelona striker Pedro Rodriguez said.
If he isn't there, you notice it. But I don't think we suffer from a dependence on Messi.
"This is a very strong team and while some players stand out, you have to recognize that Messi has gone beyond any other player. He is a key player with a great ambition, someone who wants to do better each day that goes by. We are dealing with numbers that you couldn't imagine.''
Xavi Hernandez is ready to play after being sidelined for the last two weeks with a left calf injury. Striker David Villa, however, did not make the squad after spending last week in and out of the hospital with a painful case of kidney stones. Defender Adriano will also miss the game with a right leg injury.
Assistant coach Jordi Roura will be on the sideline with coach Tito Vilanova receiving treatment in New York after having a second tumor in two years removed from his neck in December. Without Vilanova, Barcelona has avoided a major dip in form.