OBJECTIVE: To investigate the effects of pH, donor phase drug concentration and Atone on in vitro skin permeation of dihydroetorphine hydrochloride(DHE)using excised abdominal Zaocys dhumnades(Cantor ) skin. METHODS: The DHE permeation study was carried out using modified Franz-type vertical diffusion cells with an effective diffusional area of 2.5 cm² .Samples of 100μl were with drawn from the receptor solution at appropriate time intervals over 24 h and assayed for DHE by liquid scintillation method. RESULTS: The influence of pH on the permeation of DHE was very complex. The permeation flux at pH 3 and 9 was significantly faster than that at pH 5 and 7. The permeation flux at different DHE concentrations was rather steady, so the DHE permeated was in direct proportional to DHE concentrations of the selected DHE concentrations. Atone had a strong effect on the DHE permeation. CONCLUSION: The different factors that affect DHE permeation through Zaocys dhumandes skin were tested. It was found that the factors like pH, drug concentration and enhancer had intricated effect on DHE permeation. The results were useful for further research of DHE transdermal delivery system.