The world's largest museum complex will roll out the red carpet Thursday for stars including Stiller, Adams, Robin Williams, Owen Wilson and Hank Azaria.
Claire Brown, a spokeswoman for the Smithsonian's National Air and Space Museum says staffers are buzzing about the attention from the movie, a sequel to 2006's "Night at the Museum."
"We really wanted to expose kids to what the Smithsonian has to offer," she said, noting the Wright brothers' original 1903 airplane, which hangs in the museum, will fly again on screen. Other historical characters and artifacts will come to life as well.
It's the first major Hollywood premiere at the Smithsonian.
In the film, Stiller's character, security guard Larry Daley, comes to Washington to find his museum friends from the first movie, who had been shipped from New York to a mythical vault under the National Mall.
Director Shawn Levy gave The Associated Press a few hints last year about how the story will unfold.
"Imagine if every aircraft (in the museum) came alive, including the pilots," Levy said. He went on to reveal that famed pilot Amelia Earhart (Adams) is brought back to life.
After the first film, attendance shot up at New York's American Museum of Natural History, and Smithsonian curators hope the same thing will happen there.
The Smithsonian Institution and 20th Century Fox have inked numerous promotional deals and have plans for a slew of movie-themed products. On Wednesday, game maker Majesco Entertainment Co. released the first video game to explore the halls of the Smithsonian after dark, following the movie's plotline.
The movie opens nationwide May 22.
On the Net:
Night at the Museum Movie: http://www.nightatthemuseummovie.com/