We assessed the effects of FK506 administration on regeneration after 5-mm gap repair with a collagen guide seeded with syngeneic Schwann cells in the rat sciatic nerve. Functional reinnervation was evaluated by non-invasive methods to determine recovery of motor and sensory functions in the hindpaw over 4 months postoperation. Histological analysis of the regenerated nerves was performed at the end of follow-up. Treatment with FK506 (1 mg/kg for the first 2 months) resulted in significant improvement of the onset and the degree of reinnervation. The numbers of myelinated fibers in the distal regenerated nerve were similar between treated and control groups. In conclusion, FK506 improves functional recovery after repair with collagen guides seeded with syngeneic Schwann cells.