OBJECTIVE:To study the percutaneous permeability of Hydrocortisone cream with different substrates in diabetic model rats. METHODS:The Hydrocortisone O/W(oil/water)cream,water-soluble cream and oil-soluble cream were respectively prepared. Wistar rats were randomly divided into normal control group and model group. Model group was given streptozotocin(40 mg/kg)to reproduce diabetic model. Franz diffusion cell percutaneous test and HPLC were used to detect the percutaneous permea-bility rates of Hydrocortisone O/W cream,water-soluble cream and oil-soluble cream in rats of 2 groups. RESULTS:Compared with normal control group,the percutaneous permeability rates of Hydrocortisone O/W cream and water-soluble cream were obvi-ously increased,with significant difference(P<0.05);there was no significant difference in the percutaneous permeability rate of oil-soluble cream (P>0.05). CONCLUSIONS:Hydrocortisone O/W cream and water-soluble cream are easier to go through the skin of diabetic model rats,and Hydrocortisone oil-soluble cream is hard.