Introduction: little is known about the potential effects induced by sulphonylureas independently of their anti-hyperglycemic action. The present study examined the effect of glimepiride treatment on the progression of renal histological changes in diabetic rats to determine whether therapeutic intervention with these agents would prevent the onset and progression of renal complications or not. Material and methods: forty-eight adult male albino rats were equally divided into four groups; control, normal rats receiving glimepiride, streptozotocin induced diabetic non-treated rats and glimepiride-treated diabetic rats. Blood glucose level measurement and histological evaluation of renal tissue elements using H&E, Masson trichrome, and PAS reaction techniques at four and eight weeks after treatment were performed. Stained sections were subjected to some morphometric measurements namely, glomerular tuft area (GTA), mesangial matrix index (MMI) and area per cent of connective tissue (CT). Statistical analysis for significance of obtained data was performed using analysis of variance and student-T test. Results: Glimepiride did not cause any histological renal impairment when used solely. Induction of diabetes had a significant negative impact on renal structure. In addition to significant elevation of blood glucose levels, increased kidney and kidney to body weight ratio was estimated. A variety of histological changes affecting the glomerular and tubular elements of renal tissue were detected and were more intense in the eighth week of the experiment. A significant increase in GTA, MMI and area per cent of C.T. were also found in diabetic rats. All the tested parameters showed a significant improvement in the glimepiride-treated group. Conclusion: glimepiride could attenuate most of the histological changes produced in case of experimentally induced diabetic nephropathy in spite of persistent hyperglycemia. Recommendation: glimepiride could be used in Type I and type II diabetics to protect or slow down the progression of diabetic nephropathy.