We previously obtained evidence that in rats the neurons in the suprachiasmatic nucleus (SCN) receiving retinal neural inputs may be involved in the regulation of glucose metabolism. In this study we examined whether the SCN neurons containing vasoactive intestinal peptide (VIP)-like immunoreactive substance (VIP neurons) are involved in its regulation. We found that the hyperglycemic and hyperglucagonemic responses to intracranial injection of 2-deoxy-D-glucose (2DG) were synergistically enhanced by intracranial administration of VIP, and that these responses were significantly suppressed by treatment with anti-VIP antibody. These results suggest that VIP has a permissive effect on the hyperglycemic and hyperglucagonemic responses to 2DG, and thus that the VIP neurons in the SCN are probably involved in the regulation of glucose metabolism.