Former Atletico and Argentina midfielder Simeone had a two-year spell at Inter Milan, who share the giant stadium with their Serie A rivals, between 1997 and 1999.
He scored in two derbies against Milan, netting the opening goal in a 2-2 draw in November 1997 and two more in Inter's 3-0 victory in March 1998.
"I spent two extraordinary years here," Simeone said at a news conference before his squad trained on the San Siro pitch on Tuesday.
"I left behind a lot of team mates, friends and memories," added the 43-year-old, who took over as Atletico coach at the end of 2011.
"Coming back to play here is an emotional experience. I know the San Siro atmosphere.
"Any footballer in the world wants to play in a stadium like the San Siro."
Europe's elite club competition can throw up some dull first legs when it reaches the knockout stage, with neither team prepared to take risks.
However, Simeone said he expects an eventful match featuring two teams that like to attack.
"I expect an open match with a lot of chances," he said.
"For the people watching on television it's always more entertaining if it's an open match and it fits with the style of both teams," he added.
"I expect the best of Milan. They have dangerous players down the wings with an effective game between the lines in the middle and they are also very good at set pieces."
Milan, the seven-times continental champions, have struggled in recent seasons and are ninth in Serie A, 31 points behind leaders Juventus.
They sacked coach Massimiliano Allegri last month and replaced him with former Milan and Netherlands midfielder Clarence Seedorf, the only player to win the Champions League with three different clubs.
Atletico, by contrast, have had an excellent season and are level on points at the top of La Liga with Spanish heavyweights Barcelona and Real Madrid.
They are seeking a first quarter-final appearance since 1997, when Simeone played for Atletico.
"We are facing a powerful Milan, which has had some extremely important achievements," Simeone said. "But Atletico is also a team with history."
The second leg is at Atletico's Calderon stadium on March 11.
- Sports & Recreation
- Inter Milan
- San Siro