Objective To study the changes of islet beta-cell morphology and function after lifestyle intervention and administration of dpp-4 inhibitor (MK0626) in HFD induced kkay mice. Methods 1. Establish models of prediabetes-hyperinsulinism by administrating HFD in kkay mice. 2. 5 weeks old male HFD induced kkay mice were divided randomly into: kkay normal diet(KN) group, kkay high fat diet(KH) group, kkay exercise(KE) group, kkay DPP-4I(KD) group and C57BL/6J served as normal control(CN) group. During 8 weeks intervention, general features were collected weekly, FINS measurement, OGTT and IPITT were performed at 7w and 15w respectively. 2. Analyzed morphology, proliferation and apoptosis in islet beta-cell；3.Evaluated the expression of PDX-1 and MafA. Results 1. 5 week-old kkay mice will be proper models for the study after 2 weeks of HFD. At 15 weeks old, general conditions, glucose tolerance, insulin sensitivity and Islet morphology were improved in KE group and KD group. 2. Propotion of ki67 positive cells in intervention groups were higher than other groups (P < 0.01). Apoptosis were no significant differences among these groups. 3. Expression of MafA were increased in intervention groups. There were no significant difference in the expression of PDX-1. Conclusion 1. it is a proper kkay mice model of prediabetes-hyperinsulinism by early administrating HFD; 2. early intervention of life style and administration of MK0626 could delay the onset of diabetes. 3. There were no obvious changes in the expression of PDX-1 at early stage of diabetes in kkay mice. MafA may play a crucial role in the development of diabetes in this model.