The accident occurred around 6:30 p.m. on the northbound lanes of I-95 just north of Rt. 452 in Upper Chichester.
One of the vehicles involved overturned due to the impact of the crash.
Rescue units were able to get two injured people to Crozer-Chester Medical Center. They are in unknown conditions.
The northbound lanes were blocked for close to 45 minutes.
Pennsylvania State Police are investigating.