Background:Diabetic nephropathy is one of the most dangerous complications of diabetes. SGLT2 I (Dapagliflozin) are new medications for the treatment of hyperglycaemia in adults with T2DM. Their mechanism of action depends on decreasing glucose renal threshold, which leads to an increase of urinary excretion of glucose leading to a mild osmotic diuresis. Aim of work:Compare the effect of Dapagliflozin versus insulin on experimentally induced diabetic nephropathy in albino rats using biochemical, histopathological and immunohistochemical parameters. Materials and methods: We induced type 1 diabetes by single intraperitoneal injection of streptozotocin (50mg/kg). Thirty-two rats were utilized in this study and randomly divided into 4 groups (8 rats each); group I (control) group, group II (diabetic) group, group III (DM & insulin) and group IV (DM & SGLT2 I). Insulin and Dapagliflozin were given by orogastric tube in a dose of 1mg/kg/day for 8 weeks after the establishment of diabetic nephropathy. Blood samples were used for the detection of blood glucose, serum urea and creatinine. Kidney specimens were homogenized and used for the detection of oxidative stress markers [malondialdehyde (MDA) and reduced glutathione (GSH)]. Kidney specimens were subjected to paraffin sections and used for H&E, PAS and immunohistochemical staining for Alpha smooth muscle actin (α SMA). Results: Treatment with Dapagliflozin was associated with improvement in the blood glucose, serum urea, serum creatinine, serum MDA, urinary protein, urinary glucose level, serum insulin and serum GSH level. Dapagliflozin suppressed fibrosis in the interstitium of the kidney to a greater extent than insulin. Conclusion: The administration of Dapagliflozin significantly improves the diabetic nephropathy induced by STZ.