Dietary antioxidant compounds such as bioflavonoids may offer some protection against the early stage of diabetes mellitus and the development of complications. We investigated the effect of citrus bioflavonoids on blood glucose level, hepatic glucose-regulating enzymes activities, hepatic glycogen concentration, and plasma insulin levels, and assessed the relations between plasma leptin and body weight, blood glucose, and plasma insulin. Male C57BL/KsJ-db/db mice (db/db mice, 5 wk old), an animal model for type 2 diabetes, were fed a nonpurified diet for 2 wk and then were fed an AIN-76 control diet or the control diet supplemented with hesperidin (0.2 g/kg diet) or naringin (0.2 g/kg diet). Hesperidin and naringin supplementation significantly reduced blood glucose compared with the control group. Hepatic glucokinase activity and glycogen concentration were both significantly elevated in the hesperidin- and the naringin-supplemented groups compared with the control group. Naringin also markedly lowered the activity of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase compared with the control group. Plasma insulin, C-peptide, and leptin levels in the db/db mice from the 2 bioflavonoid-supplemented groups were significantly higher than those of the control group. Furthermore, plasma leptin was positively correlated with plasma insulin level (r = 0.578, P < 0.01) and body weight (r = 0.541, P < 0.05), and was inversely correlated with the blood glucose level (r = -0.46, P < 0.05). The current results suggest that hesperidin and naringin both play important roles in preventing the progression of hyperglycemia, partly by increasing hepatic glycolysis and glycogen concentration and/or by lowering hepatic gluconeogenesis.