The A6 in Barton has been closed as emergency services deal with a fire at the Boar's Head.
Police say they are assisting firefighters by closing the A6 in both directions, from the junction with Station Lane and Jepps Lane.
They have asked motorists coming from the M6 and M55 to avoid the area if possible and allow extra time for journeys.
A spokesperson for Lancashire Fire and Rescue said that the size of the fire meant "damping down" could take firefighters hours.
They warned that the A6 in Barton could remain closed for several hours just as rush hour approaches.
Just after 6.30pm, Lancashire Road Police said they had no ETA as to when the road would reopen.