Many patients with type 2 diabetes mellitus develop hypertension, although the actual mechanism remains unknown. To clarify possible mechanisms of hypertension development in diabetes, this study investigated the acute or chronic influence of hyperinsulinemia and/or hyperglycemia on the function of perivascular nerves, which play a critical role in vascular tone regulation. Acute hyperinsulinemia in euglycemic pithed rats, which had no autonomic flow, significantly augmented adrenergic nerve-mediated pressor responses and inhibited calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerve-mediated depressor responses. To increase blood glucose levels without changing serum insulin levels, pithed rats were treated with octreotide. In this model, acute hyperglycemia produced only marked enhancement of adrenergic nerve-mediated vasoconstriction. Chronic hyperinsulinemia in insulin resistance model rats caused significant increases in the function and distribution of perivascular sympathetic nerves and decreases in those of perivascular CGRPergic nerves, resulting in the development of hypertension (insulin resistance-induced hypertension). Treatment with pioglitazone or functional foods with an insulin resistance-improving effect prevented the development of insulin resistance-induced hypertension. The present studies suggest that acute and chronic hyperinsulinemia reduces vasodilator function of perivascular CGRPergic nerves and enhances the vasoconstrictor function of perivascular adrenergic nerves, leading to the development of hypertension. The results also indicate that hyperinsulinemia and hyperglycemia may have a crucial role in the alteration of neuronal vascular tone regulation.