The purpose of this experimental study was to investigate the effects of topical applications of hyaluronic acid on peripheral nerve scarring and regeneration in an adult rat model. After the right sciatic nerves of 48 rats were transected and immediately repaired, nerves were randomly divided into two groups. Nerves to which were applied hyaluronic acid comprised the experimental group, and nerves to which were applied saline comprised the control group. Perineural scarring was evaluated at 4 and 12 weeks macroscopically and histologically. Nerves treated with hyaluronic acid demonstrated significant reduction in perineural scar thickness (P < 0.05, Student's t-test). Histomorphologic nerve analysis, electrophysiologic studies, muscle mass evaluation, and serial functional walking-track analysis were performed for evaluation of peripheral nerve regeneration at 12 weeks. The results showed better conduction velocities, increased axon-fiber diameter, and faster functional recovery in hyaluronic acid-treated nerves (P < 0.05, Student's t-test). In conclusion, hyaluronic acid appears to be effective in preventing perineural scar formation, resulting in enhancement of peripheral nerve regeneration. (C) 2003 Wiley-Liss, Inc.