Malar et al.: In vivo Antidiabetic Activity of Stem Extracts of Salacia oblongaSalacia oblonga (Celastraceae), a traditional ayurvedic herbal plant commonly called as ponkoranti. The antidiabetic and Histopathological studies of aqueous stem extracts of Salacia oblonga carried in Streptozotocin-nicotinamide induced diabetic rats which were orally treated with glibenclamide and Salacia oblonga stem extracts at lower (250 mg/kg) and higher (500 mg/kg) concentrations. The normal rats were administrated for the oral glucose tolerance test at 0, 30, 60 and 120 min after glucose load. Fasting blood glucose levels were measured by glucose oxidase strips and glucometer. The protective effect was evaluated by studying the effect of antioxidant enzymes, lipid peroxidation and Histopathological changes after the treatment period. Treatment done with 500 mg/kg of stem extract produced more effect with improved protein (1.18±1.45 mg), superoxide dismutase (229.15±1.52 U/mg protein), Catalase (19.51±1.35 U/min/mg protein), Glutathione (1.54±.29 U/min/mg protein), Glutathione peroxidase (1.74±1.56 U/min/mg) and reduced lipid peroxidation (1.76±2.31 µm/min/mg). From the study, it was found that the stem extracts potentially increase the antioxidants and reduced the lipid peroxidation. The rats which were treated with Salacia oblonga and glibenclamide significantly reduced the glucose level (p<0.001). Histopathological alterations were restored after the treatment with stem extracts of Salacia oblonga at lower and higher concentrations. The significant effect on the vital organs such as liver and pancreas demonstrates the herbal usage of potential endangered plant. The spectral analysis (gas chromatography-mass spectrometry) explored the potential natural chemical constituents which were responsible for the antioxidant and antidiabetic activity. Further preclinical and clinical trials are required to confirm the potential of Salacia oblonga stem extract.