Vasopressin (VP) is a peptide consisting of 9 amino acids which acts as a neurotransmitter or neuromodulator in the central nervous system. Neurons containing VP project to some nuclei in the hypothalamus that have a role in energy metabolism. To clarify the possible role of VP on glucose metabolism in the brain, we examined the effect of intracranial injection of VP on the hyperglycemia induced by 2-deoxy-d-glucose (2DG) and obtained the following results. The hyperglycemic and hyperglucagonemic responses induced by 2DG were significantly suppressed and enhanced by co-injections of VP and a VP-antagonist with 2DG, respectively. However, co-injections of either VP or a VP-antagonist with 2DG had no effect on the change in plasma insulin concentration. These findings suggest that central VP plays a suppressive role in the hyperglycemic and hyperglucagonemic responses to 2DG.