Objective To investigate the velvet antler polypeptide (VAP) on sciatic nerve regeneration in rats through local administration and VAP-PLGA compound membrane. Methods The 3, 15 mg/g of VAP-PLGA compound membranewere prepared by compounding VAP and PLGA, respectively. Seventy-two Wistar rats, male or female, aged 3-6 months and weighing (250 ± 50) g, were selected to make the model of sciatic nerve section. Then, all rats were randomized into 4 groups (n=18): group A in which nothing was given after anatomosis, group B in which 1 mL of VAP at the concentration of 10 mg/L was injected into the gastrocnemius muscle medial for every other day, group C in which 3 mg/g of VAP-PLGA compound membrane was given to the nerve anastomotic stoma and group D in which 15 mg/g of VAP-PLGA compound membrane was given to the nerve anastomotic stoma. The sciatic adhesion degree observation, electrophysiological examination, immunohistochemical staining and hemi-quantity calculation and horseradish peroxidase (HRP) retrograde tracing were conducted 2, 4 and 6 weeks after operation, respectively. Results All rats survived to the end of the experiment, without foot ulcer or neuroma. Severer nervous adherence was observed in group A, mild adherence in group B, and no adherence in groups C and D 2, 4 and 6 weeks after operation, respectively. The recovery rate of the evoked potential of triceps surae in groups B, C and D was better than that in group A (P lt; 0.01), group D was superior to groups B and C (P lt; 0.05) at each time point. No significant difference between group B and group C (P gt; 0.05) 2, 4 weeks after operation was detected, but group C was superior to group B (P lt; 0.05) 6 weeksafter operation. For the regenerative fiber axon and the expression of myelin sheath TGF-β1 and IGF antigen, the staining intensity in groups B, C and D was higher than that in group A at each time point (P lt; 0.05), and there were significant differences between group D and groups B and C 6 weeks after operation (P lt; 0.05), but no difference between groups B and C (P gt; 0.05). The HRP retrograde tracing showed that the myelinated nerve fiber stained by HRP gradually increased as time passed by and myelinated nerve fiber stained by HRP in groups B, C and D was much more than that in group A, and group D was superior to the other groups. No significant difference between group B and group C was detected. Conclusion To apply VAP through either local administration or VAP-PLGA compound membrane around the attached site of nerve anastomosis is capable of promoting nerve regeneration, which has an obvious dose-effect relationship with the dose of VAP. Meanwhile, VAP-PLGA compound membrane can prevent the nerve adhesion.