The woman, 25, was driving south on the Henty Highway, south of McKenzie Creek Bridge, when her car ran off the road and hit a tree after 4pm on Monday.

She was the only occupant of the car.

An air ambulance crew flew the woman to The Alfred in Melbourne.

An Ambulance Victoria spokeswoman said the woman sustained a serious leg injury.

State Emergency Service volunteers worked to free the woman from the car after she was trapped by her legs.

The woman was conscious and breathing.

Horsham Sergeant Dale McIvor said police were still investigating the cause of the crash, but driver distraction might have been a factor.

He said the woman had not been wearing a seatbelt and it appeared that she had not tried to correct her vehicle.

Police directed traffic around the scene.