Mirren, 67, won an Academy Award in 2007 for Best Actress for her role in "The Queen," written by Peter Morgan.
Morgan and producers recently approached Mirren to play the role for his latest project, a play about confidential meetings between the queen and British prime ministers during the past 60 years, The Daily Telegraph reported.
"I certainly don't want to be known as the actress who played the queen, so there was a slight sense of apprehension about that element," Mirren said.
She said she made her decision after meeting with Morgan, designer Bob Crowley and the show's producers.
"I thought: 'Here are some of the best people at what they do in the world. If you don't do it, you're an absolute idiot!' So here we go again," she said.
"The Audience" will premiere in February at the Gielgud Theatre in London and is expected to run until mid-June 2013, The Daily Telegraph reported.