INTRODUCTION: Calcium overload plays a vital role in axon degeneration after nerve injuries. This study observed the effects of verapamil, a calcium channel blocker, on promoting motor functional recovery in peripheral nerve injury. METHODS: A 1 cm segment of rat sciatic nerve was compressed using a specially designed device. A pilot study was performed in 26 rats to determine the dose-reaction of verapamil (0.1 mg/kg to 6 mg/kg) on nerve functional recovery. An additional 48 rats were divided into 3 groups: Group A received a compression load of 100g for 2h, mimicking ischemia/reperfusion (I/R) insult; Group B received a 1000g load for 2h (combined I/R and mechanical insult); and Group C received a 10kg load for 5min (mechanical insult), respectively. In each group, rats were further subdivided into experimental and control groups, half receiving verapamil and the other half receiving normal saline intravenously before removing compression. Walking track testing was performed and the sciatic function index (SFI) was measured between day 1 and day 60 postoperatively (0 indicates normal nerve function and -100 represents complete dysfunction). RESULTS: The pilot study showed that the optimal dose of verapamil was 1 mg/kg, which was subsequently used. There was a significantly earlier recovery of motor function in the verapamil-treated animals over controls in Groups A and B, but not in Group C. In Group A verapamil-treated animals, the SFI recovery began at day 7 (SFI = -91.6) and rapidly increased from -75.0 to -6.2 between day 11 and day 25, which was a significantly (p<0.01) more rapid recovery than that in controls (-96.1 and -20.4). In Group B, recovery was evident after day 14. The SFI in the verapamil-treated group rapidly increased from -59.6 to -14.5 between day 18 and day 35, significantly (p<0.05) superior to controls (-91.5 and -33.8) from day 18 to day 60. In Group C, the motor functional recovery began at day 11, when SFI was -96.9, and reached -12.8 at day 25 postoperatively. There was no statistically significant difference in the SFI between the experimental and control groups in Group C at any time point. CONCLUSION: The results show that verapamil effectively improves motor functional recovery in rat sciatic nerve I/R injury (Group A), but not in mechanical injury (Group C). Verapamil may maintain calcium homeostasis during such an injury through blocking calcium channels. This has implications for treating patients with peripheral nerve injury related to I/R injury.