Objective: Prosopis Juliflora is a plant that reported to have anticonvulsant, antimicrobial, antiulcer, and wound healing activities. Diabetes effect of prosopis juliflora leaves is not clear. Hence current study planned to evaluate the antidiabetic effects of methanolic extracts of leaves of Prosopis juliflora in streptozotocin induced diabetic rats. Materials and Methods: Phytochemicals were determined by standard method. Diabetes was induced by injecting a single dose of STZ (55mg/kg) into female Sprague Dawley rats. After 3 days of induction of diabetes the diabetic animals were treated for 28 days with MEPJ (400mg/kg) and glibenclamide (20mg/kg) orally. The body weight of rats and blood glucose levels were monitored at regular intervals during the experiment. At the end of the study blood sample was collected from all the animals and subjected to biochemical parameters and they were sacrificed and their organs such as pancreas liver and kidney were used for histopathological analysis. Results:Blood glucose levels presented near 100 mg/dL in control groups. In the diabetic groups, glucose levels were higher than 300 mg/dL. The treatment with MEPJ extract did not interfere significantly with the glycaemia of control or diabetic groups compared with their corresponding groups. The animals of control and treated groups showed no difference in body weight, water and food intake during the study. The body weight in diabetic groups was statistically lower compared to control on days 14 and 20. In addition, the plant treatment caused a reduction in the body weight compared to the diabetic group (non-treated) on days 14 and 20. The rats from diabetic groups presented higher food intake (around 30 g/day) in relation to control groups (about 16 g/day) in all experimental period. In addition, the average water intake was increased in diabetic groups as compared to non-diabetic groups.