La Rue will appear this summer in several episodes of the soap opera, which began in 1970 and will wrap up its final season in September.
The actress played the role of Grey from 1993 to 1997 and again from 2002 to 2005. She last guest-starred on the show in 2010.
"From the very beginning, Maria Santos Grey stole the hearts of viewers, and is best known for her fairytale romance with Edmund Grey [played by John Callahan,]" the network said in a news release. "Together the super-couple struggled to build a family of their own while La Rue's character endured many ups-and-downs."
La Rue currently appears weekly on "CSI Miami." She is to return to "All My Children" July 19, ABC said.