Grape seed procyanidins (GSPCs) are bioflavonoid polymers that have been shown to have health benefits. We assessed the antidiabetic effect of GSPC in mice. Mice with streptozotocin(STZ)-induced diabetes were orally or intraperitoneally administered saline or 40-100 mg GSPC/kg BW daily for 7-10 d. We monitored body weight, blood glucose levels, amounts of food and water consumed, and amounts of urine and feces excreted. On the final day, we analyzed plasma chemistry and found that GSPC, but not structurally related monomers (e.g., catechin and epicatechin), reduced the glucose levels, food and water intake, and urine and feces excreted, all of which had increased due to STZ administration. This suggests a procyanidin-dependent effect of grape seed polyphenols on diabetes. Oral administration of GSPC was less effective within 9 d than was intraperitoneal administration of GSPC, suggesting that the effect is routedependent. The decrease in diabetic blood glucose levels was reversible; when GSPC administration was stopped, glucose levels rose. However, although pretreatment with GSPC for 7 d did not completely prevent STZ-induced diabetic effects, it rapidly reduced them. Treatment with GSPC reduced fasting glucose levels and improved glucose tolerance in STZtreated mice, in addition to decreasing STZ-stimulated levels of plasma triglyceride and cholesterol, creatinine, uric acid, and alkaline phosphatase activity. Moreover, GSPC suppressed the reduction in pancreatic islets and the decrease in plasma insulin hormone levels caused by STZ. Our findings indicate that GSPC improves hyperglycemia, polydipsia, polyuria, and polyphagia in mice with STZ-induced diabetes.