Two people had to be cut free by firefighters after their car left the M55 and plunged down an embankment.
One of the occupants, a woman, was said to be suffering from "serious" injuries and was rushed to the Royal Preston Hospital.
The second person in the vehicle suffered only minor injuries.
Fire crews were called to the incident between junction 1 at Broughton and junction 3 for Kirkham at around 3am today.
A fire brigade spokesman said: "There was one vehicle involved. It had left the motorway and gone down the banking.
"Two people were trapped in the car and were released by firefighters.
"One female was taken to hospital with serious injuries. I gather the other person had only minor injuries."
Officers from Highways England closed lanes one and two of the motorway for around an hour while the rescue operation was underway.