Abstract: OBJECTIVE To study the effect of blood glucose fluctuation on renal pathological changes in diabetic GK rats. METHODS Five male Wistar rats were set as normal group. Ten male GK rats were randomly divided into diabetic group and blood glucose fluctuation group based on body weight and blood glucose level, five rats in each group. In the glucose fluctuation group, intraperitoneal injection of glucose and subcutaneous injection of insulin resulted in a daytime blood glucose fluctuation model for 6 weeks. Normal and diabetic group were intraperitoneally injected with the same daily dose of normal saline for 6 weeks. The general signs of the rats were observed daily, the body weight of the rats was weighed every week, the blood glucose levels at 9 time points were measured at the 6th weekend. The glycosylated hemoglobin value(GHb) was measured at the 3rd and 6th weekends and the 24 h urine was collected at the 6th weekend. Biochemical method was used to detect urine creatinine (U-CREA), total urinary albumin(U-ALB), calculate 24 h urinary protein excretion rate(UAER). After 6 weeks, rats were executed after anesthesia, blood was taken from the heart, and blood urea nitrogen(BUN), manual detection of serum superoxide dismutase (SOD), malondialdehyde(MDA) and glutathione peroxidas(GSH-Px) in serum were detected by biochemical method. Taking kidneys, weighing, calculating renal hypertrophy index, the kidney was placed in neutral formaldehyde, PAS staining, pathological changes were observed under light microscope. RESULTS Compared with diabetics group, GHb, U-CREA, UAER, serum BUN and MDA and renal hypertrophy index in blood glucose fluctuation group was significantly increased (P<0.05), the weight gain rate, serum SOD and GSH-Px were significantly decreased (P<0.05), and renal glomerular injury and structural changes were more obvious. CONCLUSION Blood glucose fluctuation can aggravate renal lesions in diabetic GK rats, which mechanism may be related to increased MDA levels and decreased levels of SOD and GSH-Px.