Objective To observe the dynamic blood glucose levels caused by diet-induced weight gain or loss.Methods Eight-week-old male C57BL/6 mice were fed a high-calorie diet (60% fat) for 8 weeks, and then divided into an intervention group (IT) and an obesity group (OB). Mice in the OB group were fed a high-calorie diet throughout the study.A normal control group (CON) was also established and given normal chow. Limiting caloric intake reduced the weight of the IT group to that of the CON level ( P > 0. 05), after that resuming high-calorie feeding until the body weight rise back to the OB level ( P > 0. 05). Intraperitoneal glucose tolerance test (IPGTT) was performed to evaluate blood glucose metabolism,insulin tolerance test (ITT) for insulin sensitivity, and HE staining of the pancreas for islet morphological study. Results When IT group mice were again exposed to a high-calorie diet, body weight growth and fasting blood glucose rate were 2. 27times and 5. 13 times, higher than those before caloric restriction. At the end of the intervention, larger area under the blood glucose curve of IPGTT ( P < 0. 05), decreased insulin sensitivity ( P < 0. 05), larger body fat depots ( P < 0. 05), and smaller islet area were detected in comparison with those in the OB group. Conclusion Body weight fluctuations lead to an increased intraperitoneal fat mass, decreased insulin sensitivity, and impaired glucose tolerance.