The actress has appeared on the show since its first season in 2017.
"After much thought, I felt I had to step away from The Handmaid’s Tale at this time," Bledel's statement read. "I am forever grateful to Bruce Miller for writing such truthful and resonant scenes for Emily, and to Hulu, MGM, the cast and crew for their support."
Variety was the first to report the news of Bledel's Handmaid's Tale exit.
Bledel starred on The Handmaid's Tale as Emily/Ofglen since the show's first season in 2017. She earned four Emmy nominations and one win for her work on the series.
Season 4 of the Hulu series, which aired its finale in June 2021, concluded with Bledel teaming up with June (Elisabeth Moss) and other former handmaids to get revenge on Gilead.
It's currently unclear how Bledel's exit will be addressed on the show.