Objective To detect the effects of rosiglitazone and metformin on phosphatase and tension homologue deleted on chromosome 10 (PTEN) protein expression in liver and skeletal muscle tissues of insulin resistant diabetic KKAy mice.Methods KKAy mice were fed high fat diet for 4 weeks to prepare diabetic models,which were then randomly divided into 3 groups: diabetic group,rosiglitazone treatment group 12.5 mg/(kg·d),and metformin treatment group 3 g/(kg·d).C57BL mice of 16-week old,fed normal diet,served as control group.After 4 weeks,the mice were sacrificed.Expressions of PTEN protein and phosphoserine Akt in liver and skeletal muscle tissues were determined by Western blot and analyzed quantitatively by gel image analysis instrument.Results Insulin-induced phosphoserine Akt increase in liver and skeletal muscle tissues was not significantly different among rosiglitazone treatment group,metformin treatment group,and KKAy diabetic mice (P>0.05).PTEN protein expression in liver and skeletal muscle tissues was without significant difference among rosiglitazone treatment group,metformin treatment group,and KKAy diabetic mice (P>0.05).Conclusion Rosiglitazone and metformin may not exert any effect on the activity of PI3K-Akt pathway and PTEN protein expression.Their roles in improving insulin resistance and decreasing glucose may be not related with the PTEN expression in insulin sensitive tissue.