Abstract: To evaluate the influence of hot melt pressure sensitive adhesive(HMPSA) on drug percutaneous absorption，methyl salicylate and diphenhydramine hydrochloride were selected as the model drugs. Drug loaded matrix was prepared by hot melt method. Accumulated permeation amount and steady flux were obtained by Franz diffusion cell and were used to evaluate the skin permeation profiles of the two drugs. The results showed that percutaneous absorption of methyl salicylate was significantly influenced by compositions and structures of the matrix, while diphenhydramine hydrochloride was not. Conclusions could be drawn that for methyl salicylate, skin permeability of the drug loaded matrix was controlled by the drug diffusion rate in matrix for its high affinities to skin. But for diphenhydramine hydrochloride, diffusion through skin was the rate limit step and PSA matrix contributed less to the diffusion influence.