The 53-year-old actress, who plays Catherine Willows, will bid farewell in a two-part episode, one of which was shown in the US on Wednesday night, and the other to be broadcast on January 25.
Marg said she was looking forward to time off, hiking with her dog and even looking for work - and would also love to do Broadway.
Despite her departure, the actress said she would be willing to return for a special episode or two in the future.
"Oh, absolutely, in fact that was one of the reasons why it was a little easier for me to leave the show because the producers said to me practically every day the door is wide open. If I'm available and I'm up for it you betcha," she said.
She says she is proud the show has inspired some people to become criminologists and said to fans: "You haven't seen the last of me."
She called the part "one of the best roles" she ever had and "quite a journey". Looking back at older episodes she likes to remember the crime that was solved, see who the guest stars are and marvel at some of her clothes and hairstyles. "Sometimes I go, 'What was I thinking?'," she said.
Marg has received both Emmy and Golden Globe award nominations for her work on CSI and will get a star on the Hollywood Walk of Fame on January 23.
Her son Hugh is now a production assistant on the show.
CSI is known as the most watched show in the world and has received the International Television Audience Award at the Monte Carlo TV Festival.
Copyright © 2012 The Press Association.