Previous studies have indicated that neurons containing a vasoactive intestinal polypeptide (VIP)-like immunoreactive substance (VIP neurons) in the suprachiasmatic nucleus (SCN) are involved in regulating glucose metabolism in rats. In this connection, it has been suggested that in rats, VIP neurons in the SCN have neurotensin (NT) receptors. To clarify the role of NT, we examined the effects of intracranial injection of NT and an NT-antagonist on the hyperglycemic response to intracranial injection of 2-deoxy-D-glucose (2DG) in rats. The hyperglycemic and hyperglucagonemic responses caused by intracerebroventricular injection of 2DG were significantly enhanced by intracerebroventricular co-injection of NT, but suppressed by co-injection of the NT-antagonist. Intraperitoneal injection of the NT-antagonist did not affect the hyperglycemic and hyperglucagonemic responses to 2DG. These results suggest that intracranial NT plays an endogenously enhancive role in the hyperglycemic and hyperglucagonemic responses caused by 2DG.