Pancreatic ${eta}$ cells are very sensitive to oxidative stress and this may play an important role in ${eta}$ cell death in diabetes. The protective effect of diphlorethohydroxycarmalol (DPHC), one of phlorotannin polyphenol compound purified from pae (Ishige okamurae) against high glucose-induced oxidative stress was investigated using RINm5F pancreatic ${eta}$ cells. High glucose (30 mM) treatment induced RINm5F pancreatic ${eta}$ cells cell death, but DPHC, at concentration 10 or $50{mu}g/mL$, significantly inhibited the high glucose-induced glucotoxicity and apoptosis. Furthermore, treatment with DPHC dose-dependently decreased thiobarbituric acid reactive substances (TBARS), intracellular reactive oxygen species (ROS) generation and nitric oxide level increased by high glucose. In addition, DPHC treatment increased activities of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in high glucose pretreated RINm5F pancreatic ${eta}$ cells. DPHC treatment improved the secretory responsiveness following stimulation with glucose. These findings indicate that DPHC might be used as potential nutraceutical agent which will protect the glucotoxicity caused by hyperglycemia-induced oxidative stress associated with diabetes.