Objective To observe enhancing effect of nerve regeneration on peripheral nerve defect models bridged by silicone tube idled with valproic acid (VPA). Methods In present research we demon-strate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats. An 8-mm sciatic nerve deficit was created in a rat mode land bridged by a 1-cm silicone tube.Then, 10 lad of 8% VPA were perfused into the silicone chamber in the VPA group. The same volume of normal saline was delivered in the control group. Results Each animal was observed sciatic nerve function index (SFI) at 2-week intervals and studied electrophysiology at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed at the end of the experiment, 12 weeks after operation. Using the digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity, MCV), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the VPA group and controls (P ＜ 0.05). Conclusion The results demonstrated that VPA is able to enhance sciatic nerve regeneration in rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.