"We have loved each other for a very long time and we share four incredible sons together," Gilbert said in a statement. "On behalf of our family we ask to be allowed our privacy during this very difficult time."
"The Scarecrow and Mrs. King" star, Boxleitner, 60, who was in the original "Tron" film and recently "Tron: Legacy," married Gilbert, who played Laura Ingalls on "Little House on the Prairie," in 1995.
That same year, their son Michael Garrett, now 15, was born 12 weeks premature.
You may also know Boxleitner from the NBC show "Heroes" and recognize Gilbert's voice as that of Batgirl from the animated "Batman" television series.
The two both have children from previous marriages.
-- Nardine Saad
Photo: Melissa Gilbert and Bruce Boxleitner arrive at the L.A. premiere of "Tron: Legacy" on Dec. 11, 2010. Credit: Dan Steinberg / Associated Press