Abstract: Objective To detect the expression of Foxo3a in adipose tissue from KKay diabetic mice and the effects of treatment of rosiglitazone and metformin on FoxO3a expression in adipose tissue. Aim to understand what the role they play in the mechanism of insulin resistance. Method Study group consists of 21 KKay diabetic mice fed normal diet until 12 weeks, thereafter fed high fat diet for 4 weeks. mice were randomly divided into 3 groups one group without any treatment, one gaven rosiglitazone 12.5 mg/kg qd, one metformin 3g/kg/day bid for 4 weeks. Control group consists of 7 C57BL mice 16 week old. Dispatched the mice and took adipose tissue then put on tissue lytic solution to measure the protein concentration by Bradford method and to detect Foxo3a protein expression on adipose tissue by Western Blot with multiple colony antibody 1:1250. Quantitative analysis used by gel image analyzing instrument. Results Foxo3a was higher expressed in adipose from KKAy diabetic mice than that in control group (FoxO3a/b-actin ratio 1.76 ± 0.19 vs1.15 ± 0.10，P<0.001). Rosilitazone treatment decreased the expression of FoxO3a in adipose tissue significantly compare to KKAy diabetic mice (FoxO3a/b-actin ratio 1.43 ± 0.24, P<0.05). Metformin treatment can not significantly reduce FoxO3a expression in adipose tissue1.57 ± 0.23, compared to KKAy diabetes group. Conclusion Expression of FoxO3a in adipose tissue increased in KKAy diabetic mice. Rosiglitazone decreased the blood glucose and insulin resistance may through the pathway of FoxO3a. Metformin reduces blood glucose and insulin resistance may not related adipose FoxO3a expression.