Callies' character's life and death was controversial for fans and she said she received very different reactions from men and women.
"It was a really interesting experience in gender," Callies told The Early Edition's Rick Cluff.
In the show, Grimes is separated from her husband and believing he is dead, she begins an affair with his best friend Shane Walsh.
Later in season three, she is dying during childbirth, and is shot by her 12-year-old son to prevent her becoming a zombie.
"There were legions of people who reached out to me directly — who wrote online — who loved her and who really had her back," said Callies.
"What was interesting to me demographically was by and large those people were women and sometimes they weren't even necessarily the teen viewers — they were moms going, 'Heck girl, all bets are off in the zombie apocalypse.'"
Was Lori Grimes a bad parent?
Callies said other viewers leveled rage at her character for cheating on her husband and for not always being a good parent — sometimes losing track of her son.
But Callies rejects that view.
"Lori's staying back at camp and kind of doing everything she can to keep the whole camp running and keep her son safe and Rick continually leaves both his wife and child," she said.
"It was Lori who caught the flak for being a parent who every now and again turns around can't find her 12-year-old son."
It has been two years since Callies has been on the show and she said she has moved on, as has the series.
"In a way I miss the show, but the show I miss doesn't really exist anymore … there was a group of us that started it back when nobody thought anybody would really watch and it was this crazy experiment," she said.
"All my friends are dead, is what I'm trying to say, and I think the brilliance of the show is that it continues to evolve with new characters and new people."
To hear the full interview with Sarah Wayne Callies, listen to the audio labelled: Sarah Wayne Callies on her role of Lori Grimes in The Walking Dead.