Diabetes (DM) is a group of complex and chronic metabolic disorders with diverse multiple etiologies. Long-term complications may affect organs such as kidneys, eyes, nerves, heart, and blood vessels. Solanum nigrum water leaves extract (SNWLE) are among the herbs used for controlling hyperglycemia in conventional medicine. This work was conducted to determine the possible effect of SNWLE on rat diabetes caused by streptozotocin (STZ). Forty adult male Wister rats were allocated to five groups (8 rats each) and studied for 8 weeks as the following scheme., group (I) normal control (cont. ( -)), group (II) diabetic control rats were given distilled water daily by gastric incubation (cont. (+) ), group (III) diabetic rats were treated orally with Glimepiride (GI) (1 mg/kg/day), groups (IV) and (V) diabetic rats were treated orally with SNWLE (250 mg/kg /day) and SNWLE (250 mg/kg /day) combined with GI (1 mg/kg/day), respectively. Blood samples and pancreas were collected on the last day of the experimental period (8 weeks) for biochemical parameters estimation as well as the histopathological examinations. The SNWLE and/or glimepiride administration to diabetic rats reduced significantly blood glucose (BG) level, kidneys function parameters, and MDA. On the other hand, insulin and CAT levels were significantly higher relative to cont. (+). Moreover, the extract showed significant amelioration in pancreatic and kidneys cells structure. These findings demonstrated that SNWLE might exert a treatment role against DM via its antioxidant mechanism.