Drivers are being advised to avoid the motorway following an accident near the Leyland junctions.
The M6 has been shut southbound between junctions 28 and 29. Lane three northbound has also been closed.
The crash, which involved a HGV lorry and a BMW, happened at around 9.50am.
The HGV trapped the BMW underneath it, after flipping to its side.
Lancashire Police said a female driver managed to get herself out of the BMW with minor injuries, while the lorry driver had to be extracted from his cabin.
Both drivers were taken to hospital.
Recovery of the vehicles is taking place and the southbound carriageway will remain closed while a clean-up operation is in place.
There is currently queuing traffic at junction 29 southbound.
Drivers are advised to leave the M6 at junction 30 and use the M61 as a diversion.