The series co-creator will play talkshow host Larry King, who interviews Tony Stark on live television about his new black armour.
Lee has previously made cameo appearances in numerous Marvel film adaptations, but his role in Iron Man 2 will be his most substantial to date. He also portrayed Hugh Hefner in the first Iron Man film during a red carpet scene.
Lee, scripter Larry Lieber, and artists Don Heck and Jack Kirby created the character in 1963. The superhero made his first appearance in Tales Of Suspense #39, with Lee acting as writer and editor of the book.
Iron Man 2 is released to cinemas on May 7, 2010.