Ethanolic extract of bitter fraction of Stevia rebaudiana (Srbf) was extracted to investigate its antihyperglycemic and protective effects on renal structural changes in STZ-induced diabetes. Thirty-five male mice were divided into five groups randomly; the first group as non-diabetic control, the second group as untreated diabetic, the third group treated with glibenclamide 0.5 mg/kg,and the fourth and fifth groups treated with Srbf by 200 and 400 μg/kg bw through gavage, respectively, for 15 days.Diabetes was induced in the second to fifth groups by administration of 60 mg/kg bw of streptozotocin intraperitoneally. Serum glucose level was monitored every day. Atthe 16th day, the subjects were sacrificed and their left kidneys were removed. Tissue sections were stained by periodic acid Schiff and used for stereological analysis.The means were compared by one-way ANOVA and Tukey’s post hoc test at the significance level of p ≤ 0.05.The results showed that Srbf significantly restored the blood glucose level toward normal level faster than glibenclamide. High dose of Srbf could significantly decrease the length and volume of proximal and distal tubules and vessels and the volume of the interstitial tissue in the diabetic treated group. Both doses of Srbf could significantly prevent the glomerular hypertrophy and reduction of glomerular number in comparison with the untreated diabetic group. It can be concluded that the antihyperglycemic properties of a bitter fraction of S. rebaudiana are better than glibenclamide, and at high dose, it can ameliorate structural nephropathy in diabetic mice.