We investigated the effect of Ishige okamurae extract on blood glucose level and insulin resistance in C57BL/KSJ-db/db mice. We administered a standard AIN-93G diet with or without IOE to the animals for 6 weeks. After 6 weeks, blood glucose level was improved and blood glycosylated hemoglobin levels were lowered in sample group mice as compared to those in the diabetic control group mice. Hyperinsulinemia was reduced in the I. okamurae extract group mice with type 2 diabetes. With regard to hepatic glucose metabolic enzyme activities, glucokinase activity was enhanced in the IOE group mice, while glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the IOE group mice were significantly lowered than those in the diabetic control group mice. In addition, the hepatic glycogen content was elevated in the IOE group as compared to that in the diabetic control group. The homeostatic index of insulin resistance was lower in the I, okamurae extract group mice than in the diabetic control group mice. These resuIts suggest that a dietary supplement of I. okamurae extract lowers the blood glucose level by altering the dietary supplement of I. okamurae extract lowers the blood glucose level by altering the hepatic glucose metabolic enzyme activities and improves insulin resistanse. 2011 published by Elsevier Ireland Ltd.