This study aimed to investigate the effects of aqueous leaf extract of Morus alba on biochemical and histological changes in streptozotocin (STZ)-induced diabetic nephropathy. Male Wister albino rats were divided into five groups of six each: Group 1: Control group; received citrate buffer for 10 days. Group 2: Untreated diabetic rats injected intraperitoneally with 50 mg/kg of STZ; received distilled water for 10 days. Group 3-5: Diabetic rats; received Glimepiride and M. alba in 2 dose levels (250 and 500 mg/kg) for 10 days, orally. STZ-diabetic rats exhibited hyperglycemia accompanied with increased α-amylase levels, total cholesterol (TC) and kidney function, on the other hand, reduced high density lipoprotein cholesterol (HDL-C) and total antioxidant capacity (TAC) levels. Morus alba in its 2 dose levels (250 and 500 mg/kg) showed a significant lowering effect in serum glucose, α-amylase, TC levels and kidney function as well as increasing serum HDL-C and TAC levels comparable to STZ diabetic group. Microscopic examination of the pancreatic sections and kidney of diabetic rats treated with M. alba at higher dose revealed approximately normal structure, compared with STZ diabetic group. These results indicate that treatment with aqueous extract of M. alba may be effective in STZ- induced diabetic nephropathy as it showed higher hypoglycemic and hypolipidemic properties with more down-regulation of α-amylase and restore kidney function than, reference drug, Glimepiride potancy.