Background : We have previously reported that Oligonol, a low-molecular polyphenol derived from lychee fruit, has protective effect on the liver and kidney of diabetic animal model. In this study, we examined whether Oligonol has any beneficial effects on pancreas of diabetic rats. Methods and Results : Oligonol was orally administered at a dose of 10 and 20 mg/kg body weight for 10 days to STZ-induced diabetic rats, and the effects were compared with those of vehicle-treated diabetic control and non-diabetic control rats. The administration of Oligonol reduced hyperglycemia in diabetic rats through an improvement of serum and pancreatic insulin levels. The increased reactive oxygen species levels in pancreas of diabetic control rats was attenuated by the Oligonol administration through inhibiting the expression of NADPH oxidase-related proteins. The enhanced expression of pro-apoptotic proteins in pancreas of diabetic control rats was significantly reduced by Oligonol administration through down-regulation of phosphor-c-Jun N-terminal kinases protein in pancreas. Furthermore, the expressions of cell proliferation-related protein were also augmented in Oligonol treated-diabetic rats. However, Oligonol treatment led to improved histological changes in the pancreas. Conclusion : These pancreatoprotective effects of Oligonol were achieved through attenuation of oxidative stress and its sensitive protein expression associated with apoptosis and cell proliferation in diabetic rats.