Fibrin, derived from the blood protein fibrinogen, is deposited in the sciatic nerve after injury and retards functional regeneration. Since Schwann cell migration is critical for remyelination of injured nerves, we investigated the effects of fibrin in this process. In vivo experiments showed that fibrin co-localizes with fibronectin deposition in the injured sciatic nerve. In vitro migration assays demonstrated that fibrin alone is not a permissive substrate for Schwann cell migration. Furthermore, migration assays of Schwann cells on mixed fibrin/fibronectin substrates showed that fibrin has a dose dependent inhibitory effect on Schwann cell migration on fibronectin. Our results show that fibrin, deposited in the sciatic nerve after injury, changes the composition of the extracellular matrix and inhibits Schwann cell migration. This negative effect of fibrin should be considered in the therapeutic application of biomaterials based on fibrin matrices.