Police say one of the injured, an 11-year-old boy, had to be airlifted to Alder Hey Hospital on Merseyside following the collision on the main A585 Fleetwood Road at Esprick.
The incident happened around 4pm and blocked the road in both directions. The closure is expected to be in place until around 8pm as accident investigators complete their work.
A spokesman for Lancashire Police said: “We are attending a four vehicle road traffic collision in which five people have been injured.
“We do not believe any of them has been seriously injured, although the air ambulance has taken an 11-year-old boy to Alder hey with a suspected broken leg.
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“We were called at just after 4pm and the road has been completely closed. We expect it will remain that way untiul maybe 8pm.”
Traffic diversions were put in place, but the collision caused major hold-ups for traffic in both directions.