The California Highway Patrol did not immediately confirm that a shooting had occurred.
The incident was reported shortly before 2 a.m. on the southbound side of the freeway, near University Avenue.
A witness said they heard a crash and then as many as six gunshots, according to a CHP incident log.
Officers responded to the scene and a SigAlert was issued, shutting down all lanes as an investigation got underway. Southbound traffic was backed up to the 91 Freeway.
News video from the scene showed the wreckage of a car whose rear windshield was shattered. At least two people were taken away in an ambulance in unknown condition.
The SigAlert was canceled around 6:30 a.m.