We have presented several lines of evidence suggesting that in rats the neurons in the hypothalamic suprachiasmatic nucleus are involved in the regulation of glucose metabolism. There are neurons containing vasoactive intestinal peptide (VIP)-like immunoreactive substance in the suprachiasmatic nucleus, and we thought that these VIP neurons might regulate glucose metabolism. To investigate this possibility, we examined the effect of VIP injection into the lateral cerebral ventricle or the peritoneal cavity on the blood glucose level. We found that Intracranial injection of VIP into unanesthetized rats elicited hyperglycemia and hyperglucagonemia without hyperinsulinemia, although these responses showed no photoperiodicity. We also found that intraperitoneal injection of the same dose of VIP had no effect on the plasma concentrations of glucose and insulin. These facts suggest that VIP is involved in the regulation of glucose metabolism governed by the suprachiasmatic nucleus.