Objective：To study the effects of penetration enhancers and their combinations on the transdermal delivery of fluoxetine hydrochloride and to discuss the feasibility of transdermal administration of drugs. Methods: The penetration rate of fluoxetine hydrochloride through rat skin in vitro was measured using ValiaChien diffusion cells and high pressure liquid chromatography was used for analysis. Results: Penetration enhancers,such as Azone,Nmethyl2pyrrolidone(NMP),oleic acid,and their combinations all had peneration enhancing effect except for propylene glycol(PG). Azone combined with PG or NMP had the most potent enhancing effect. Conclusion: Satisfactory penetration of fluoxetine hydrochloride through rat skin can be obtained by correct combination of enhancers.