"Grace and I have two beautiful kids together," said Tuesday the Oscar-winning actor in a statement to CNN. "We are entering a transition period in our relationship which is a difficult but constructive process".
"I pay tribute to Grace as a wonderful mother and ask for the intimacy and respect of all as we develop our roles as partners in parenthood," De Niro added in his statement.
The couple met while Hightower was working as a hostess at a Mr. Chow's restaurant and got married in 1997.
They are the parents of two children, Elliott, 20, and Helen Grace, 6.
Hightower is a philanthropist who has also played small roles in film and television.
The couple has already had marital problems. De Niro filed for divorce in 1999, but the two wishes were reconciled and renewed their wishes in 2004.
The actor was previously married to Diahnne Abbott from 1976 to 1988 and they have two children, Drena, 47, and Raphael, 42.
In 1995, he welcomed his twin sons, Aaron and Julian, with his then friend, Touki Smith.