Carissa spinarum L. is an evergreen, thorny shrub found in the Himalayan areas of Indo-Pakistan subcontinent. Number of ethno-medicinal applications of this plant has been reported. Pharmacologically this plant has been extensively used for the treatment of asthma and pulmonary diseases, anticancer, diarrhea, hepatoprotective, cardioprotective and reproductive dysfunction. Present study was aimed to study effects of Carissa spinarummethanolicleaf extract in alloxan treated mice pancreas. Mice were injected with alloxan monohydrate (150 mg/kg BW) intraperitoneally and selected diabetic mice were divided into four groups with six mice in each group. Diabetic mice were given Carissa leaf extract orally to a dose of 600 and 800 mg/kg body weight and glimepiride (2mg/kg body weight) for 28 days daily. The histopathological studies of pancreas of diabetic mice revealed degeneration of pancreatic histoarchitecture, but regenerative changes were observed after treatment with administration of Carissaspinarum leaf extract. Significant changes in activities of enzymes involved in carbohydrate metabolism i.e. G6PD, hexokinase and LDH were recorded after extract administration to alloxan induced oxidative stress in diabetic mice.