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Functional nerve regeneration after reconstructive nerve surgery remains unsatisfying. In this study, vascular endothelial growth factor (VEGF) gene therapy combined with a hyaluronic acid (HA)‐enriched microenvironment in nerve regeneration was investigated. Sciatic nerve was transected, and end‐to‐end neurorrhaphy was performed on 32 male Sprague‐Dawley rats, which were randomly divided into four groups (n = 8 per group): nerve coaptation without treatment (group I); nerve coaptation covered with HA film sheath (group II); nerve coaptation with intramuscular VEGF gene in plasmid injection (group III); and nerve coaptation combined with HA film sheath and intramuscular VEGF gene in plasmid injection (group IV). Contralateral sciatic nerves were used as control. VEGF expression was verified from gluteal muscle biopsies surrounding the sciatic nerve by reverse transcriptase‐PCR …