Objective To investigate the effects of GDNF-modified Schwann cells on the repair of sciatic nerve defects in rats. Methods Forty adult Wistar rats were randomly divided into four groups: group A (nerve grafts, fabricated by extracellular gel and PLGA conduits, n=10), group B (Schwann cells and extracellular gel and PLGA conduits, n=10), group C (GDNF-modified Schwann cells and extracellular gel and PLGA conduits, n=10), and group D (autograft, n=10). Motoneuron conduction and morphology (including anatomical measures and ultrastructure) of the regenerated axons were investigated at 12 weeks postoperatively. Regeneration rate of the motoneuron in spinal cord was also evaluated by using HRP label technique. Results Higher rate of nerve regeneration or number of labeled motoneurons in spinal cord was observed using PLGA conduits seeded with GDNF enhanced expressing Schwann cells (group C) than that with PLGA conduits (group A) alone or PLGA conduits seeded with control Schwann cells (group B), but there was no significant difference as compared with that in the autograft group (group D). Conclusion These results suggest that using gene transfer techniques to increase neurotrophic factor expression in Schwann cells added to nerve grafts may be a promising method for improving nerve regeneration.