Sympathetic vasoconstriction is susceptible to diabetes, but contributions made by purinergic neurotransmission in this state have not been investigated. We aimed to evaluate sympathetic vasoconstriction contributions by ATP and norepinephrine in tail artery from streptozotocin-diabetic rats using isometric vascular rings. Tail arteries were isolated from rats made diabetic 3 months previously with streptozotocin (diabetic group), age-matched non-diabetic rats (non-diabetic injected), age-matched untreated animals (non-injected normal) and age-matched untreated animals in high glucose control Krebs (high glucose control). Responses to KCl (60mM) or nerve stimulus trains of 1-100 impulses were identical in all groups. Electrical stimulation produced progressively greater contractions with increasing impulses numbers. These were partially reduced by suramin (100µM, P2 antagonist), NF279 (1µM, P2X blocker) and phentolamine (2µM, alpha blocker). For purinergic antagonists, blockade was greater in diabetic vessels compared to others. No differential effect could be detected for phentolamine between groups. Bath-applied ATP (1nM-1mM) and norepinephrine (0.1nM-100µM) showed increased potency with diabetic group vessels. Desipramine (1µM, norepinephrine reuptake inhibitor) potentiated neurally-evoked responses in all groups equally, and increased sensitivity to exogenous norepinephrine in a similar fashion. Histochemical labeling of sympathetic nerves with neuronal marker protein, PGP 9.5, and a sympathetic nerve-specific antibody for tyrosine hydroxylase showed no reduction in diabetic innervation density. We demonstrate for the first time, changes in contributions of ATP and norepinephrine in sympathetic responses of rat tail artery in diabetes which cannot be accounted for by axonal degeneration or by changes in norepinephrine reuptake.