Objective:To compare the effects of intermittent high blood glucose on insulin release and insulin sensitivity in GK rats. Methods:Twenty-two male GK rats were randomly divided into 2 groups,which were consistent high blood glucose group(HG) and intermittent high blood glucose group(FG). Eleven male wistar rats were used as normal glucose controls(NG). The fluctuant high blood glucose animal model was induced by intrapentoneal injection of insulin and glucose at different time for 6 weeks. After the introperitoneal injection, glucose tolerance test was performed and the animals were taken blood and the area under curve of glucose(AUCG) was calculated routinly. Then glucose stimulated insulin secretion(GSIS) test in vitro was carried out and mRNA level of pdx-1,insulin-1 and insulin-2 were determined semi-quantitatively by RT-PCR. Results:①After 6 weeks of experiment, there was no difference in body weight between FG and HG group(P > 0.05);②The fasting glucose level of FG group was higher than that of HG group(P < 0.05); After glucose charge, glucose level of the FG group at 15,30,60 and 120 min were significantly higher than those of control group(P < 0.05) and AUCG was also markedly elevated(P < 0.05);③The stimulating index of islets in vitro of HG group was significantly higher than that of FG group(P < 0.05); ④Compared with HG group mRNA level of pdx-1,insulin-1 and insulin-2 were decreased in FG group;⑤Insulin sensitivity of FG group rats was deteriorated and has a blunted glycemic response to insulin(P < 0.05). Conclusion:Continuous blood glucose variability could lead to impaired insulin releasing and deteriorated glucose tolerance and insulin sensitivity which may accelerate insulin releasing defects.