Klopp said he was making a pragmatic decision to ease the burden on his first-choice players after five matches in 15 days, with a busy festive programme also coming up.
"We have to rotate, we will rotate," said the German. "We have to rotate, that is the headline.
"The medical department would smash me if I played the same side again, so I will make changes.
"If you have fresh legs you can have higher energy levels and if you have that you have a chance to have a good game, that's exactly the idea behind it."
Mohamed Salah has scored in each of Liverpool's past six away games in Europe but Klopp refused to be drawn on whether he would start at the San Siro.
"I cannot change all the line-up," he said. "We need players on the pitch so I can't rotate and start with nine, that's not possible.
"We will see if Mo plays or not and if he plays or scores or not but the players are very understanding about the situation. We want to field the best possible side for the situation we are in."
Klopp also said he and Salah were on the same page when it came to the Egypt international's contract, which has just over 18 months to run.
Reports suggest he wants to stay at Anfield but that he believes the decision is in the club's hands.
The Liverpool boss is optimistic a deal can be struck for the 29-year-old despite the likely requirement for a significant salary increase.
"We are talking," he said. "Extending a contract with a player like Mo is not a thing you do and you meet for a cup of tea in the afternoon and find an agreement. That's completely normal. There's really nothing else to say about it."
Klopp said it was likely that Divock Origi, who scored a last-gasp winner against Wolves on Saturday, would get a run-out in Milan.
When asked about whether the Belgium international, largely used as a substitute, moaned about his lack of game time, Klopp said: "Moan is not the right word but of course he knocked on my door and we were talking about things.
"We've worked together since I've been here pretty much so that has happened from time to time but it's not about talking about things, it's about letting things happen and that for the players is the same."
He added: "If you are not a starter for Liverpool you can still be a world-class player. It's really possible."