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The aim of this study was to evaluate the influence of diabetes on the percataneous permeation and absorption of dexamethasone acetate(DA)anddexamethansone sodium phosphate(DSP),two main esters of dexamethansone inclinical practice.Our study employed histopathological method to determine thechanges of diabetic skin and used both of improved Franz diffusion cells andmicrodialysis to evaluate the percataneous permeation and absorption of DA and DSPin normal and diabetic rats.The results showed that the amount of DSP penetratingthrough the diabetic skin increased significantly compared with that through thenormal skin,whereas the amount of DA penetrating through the skin did not differsignificantly in diabetic and normal rats.In conclusion,diabetic rat s skinsignificantly increased the percataneous permeation and absorption of DSP but had noeffect on that of DA.We presumed that such an outcome may be caused by differentOctanol/water Partition Coefficient and different limiting step in the transfer throughskin of DA and DSP,so the changes of different skin layers induced by diabetes haddifferent effect on these two drugs.This study suggests that it is vital to focus on thewater-soluble drug with permeation as them rate-limiting such as DSP whennecessary administration is taken on skin after suffering from diabetic.