The anti-diabetic potential of watermelon (Citrullus vulgaris Schrad) was evaluated in vivo. ICR mice were fed experimental diet containing none, 10% watermelon flesh powder (WM-P) or 1% watermelon rind ethanol extract (WM-E). At the end of 4 weeks, mice were administrated with streptozotocin (40 mg/kg, i.p.) for 5 consecutive days to induce diabetes. Supplementation with WM-E significantly decreased blood glucose level and increased serum insulin levels. Feeding of WM-P also induced moderate changes but those were not statistically significant. Immunohistochemical analysis showed watermelon effectively protected pancreatic cells death. These results suggest that watermelon has a beneficial effect on diabetes.