Previous results have shown that IV infusion of glucose reduces feeding induced by systemic administration of 2-deoxy-D-glucose (2-DG) or 2-mercaptoacetate (MA) in rats. Because glucose is a metabolic substrate for both central and peripheral tissues, the suppression of feeding by glucose could result from either a central or peripheral metabolic effect. In the present experiment we attempted to clarify the mechanism of glucose-induced suppression of feeding induced by 2-DG and MA by administering glucose centrally during systemic metabolic challenge. Administration of glucose into the lateral ventricle was begun immediately after systemic injection of 2-DG or MA and continued intermittently during the 2-h feeding test. We found that central glucose administration significantly reduced 2-DG- but not MA-induced feeding. These results suggest that the central effects of glucose are sufficient to suppress feeding induced by systemic 2-DG and support the hypothesis that receptors responsible for 2-DG-induced feeding are located in the brain.