Abstract: Objective To detect protein PTEN in live and muscle tissue in KKAy diabetic mice and investigate whether PTEN is associated with the insulin resistance in diabetic KKAy mice. Methods: Study group was divided into normal diet C57BL group (n=7,sixteen-week-old C57BL mice) , high fat diet C57BL group (n=7), diabetic KKAy group (n=7), the latter two group were fed with normal diet until week 12, thereafter fed with high fat diet for 4 weeks. Blood glucose were measured from tail vein every week, it would be diagnosed of diabetes if blood glucose more than 300mg/dl (16.7mmol/L) in two consecutive weeks. Dispatched the mice ,took quadriceps of femoris muscle and liver tissue ,added tissue lytic solution, measured the protein concentration by Bradford method and detect the PTEN protein expression in muscle and liver tissue by Western bolts methods. Results: The PTEN protein level was significantly elevated in quadriceps muscle and live tissue in KKAy mice compared to the both age-matched C57BL control groups.(P <0.01). Conclusion: PTEN may be a potent negative modulator of the PI3K-Akt pathway and then play an important role in the development of insulin resistance.