The purpose of this study was to investigate the effects of combined application of human amniotic membrane wrapping and hyaluronic acid injection on peripheral nerve scarring in an adult rat model. After circumferential epineurectomies of right sciatic nerves were performed in each of 72 rats, nerves were randomly divided into three groups: (1) nothing was done additional to epineurectomy; (2) the epineurectomized segment was wrapped with human amniotic membrane; and (3) the epineurectomized segment was wrapped with human amniotic membrane and hyaluronic acid was injected inside. The extent of adhesions and perineurial scar thickness was macroscopically and histologically evaluated at 4 and 12 weeks. The least adhesion and perineurial scar tissue were observed in nerves treated with human amniotic membrane wrapping and hyaluronic acid injection. This combination appears to be safe and effective in preventing perineurial scar formation after peripheral nerve surgery in rats.