The present study was designed to investigate the antihyperglycemic effect of Umbelliferone (UMB) in normal and streptozotocin (STZ)-diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180-200 g, by administration of STZ (40 mg/kg of body weight) intraperitoneally. Diabetic rats showed an increase in levels of blood glucose and glycosylated hemoglobin (HbA(1c)) and activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase, and a decrease in levels of plasma insulin, hemoglobin (Hb), and liver glycogen and activities of glucokinase and glucose-6-phosphate dehydrogenase. Intraperitoneal administration of UMB (10, 20, and 30 mg/kg of body weight) and glibenclamide (600 micro g/kg of body weight) in 10% dimethyl sulfoxide dissolved in water, for 45 days, produced significantly decreased levels of blood glucose and HbA(1c) and activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase, while elevating levels of plasma insulin, Hb, and liver glycogen and activities of glucokinase and glucose-6-phosphate dehydrogenase to near normal levels in STZ-diabetic rats when compared with normal control rats. Normal rats treated with UMB (30 mg/kg of body weight) also showed a significant effect on glycemic control. Thus, our results show that UMB at 30 mg/kg of body weight possesses a promising antihyperglycemic effect that is comparable with glibenclamide.