A lorry driver was seriously injured when his vehicle hit the central reservation of the M60 motorway near the Trafford Centre.
Greater Manchester Police said the man may have suffered a medical incident before the collision about 05:30 BST and he has since been taken to hospital.
Huge delays have developed with the clockwise section between junctions 6 and 9 temporarily closed.
Diversion routes have also been put in place and motorists are urged to allow extra time for their journeys.
