Lowe plays Sen. Robert McCallister, who is married to Calista Flockhart's character, Kitty. He has appeared on the drama for four seasons.
The departure was first reported by the blog Deadline Hollywood, which quoted ABC Entertainment President Steve McPherson saying that the network was in talks with Lowe for his own show.
This isn't the first time Lowe has left a role where he's part of an ensemble. He exited NBC's "The West Wing" in 2003 to star in "The Lyon's Den." The show was canceled after six episodes aired.
The 45-year-old actor said in an interview with The Associated Press in November that he was excited to play a bad guy in the TV movie "Too Late to Say Goodbye" because it wasn't the romantic lead.
"Bad guys are always the best-written characters, they get to be more outlandish. Sometimes the hero in a romantic lead can be a little dull if not handled right," he said. "... On television, I'm usually playing the romantic lead. I certainly do on `Brothers & Sisters,' and I sort of did on `The West Wing.'"
ABC is owned by The Walt Disney Co.
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