Diabetes is associated with several cardiovascular problems, including systemic hypertension. Recent studies using the streptozotocin-induced diabetic rat model indicated increased contributions from purinergic and adrenergic sympathetic cotransmitters to responses in tail arteries (Donnelly et al. 2004). NPY is a known co-transmitter, thought previously to act exclusively via NPY-Y1 receptors in normal tail arteries (Bradley et al. 2003). In this study we used molecular and functional techniques to determine changes in expression of NPY Y1 and Y2 receptor subtypes and their contribution to vasoconstriction in diabetic rat tail arteries. Sprague-Dawley rats (8 weeks, male) were made diabetic by injection (60mg kg^-1, i.p.) of streptozotocin, and maintained for 12 weeks. Animals having a blood glucose with values >10 mM were deemed diabetic (n=9, blood glucose 39±2 mM). Tail arteries were excised after animals had been killed and RNA extracted (1 preparation from 2-3 vessels). Expression of NPY receptor subtype mRNA was determined by real time PCR normalized to GAPDH mRNA. In control tail arteries, NPY Y1 was expressed more abundantly than NPY Y2 mRNA (mean±SEM, cycle times (Ct) for tail arteries 30.4±0.3 and 33.5±0.6, n=2). NPY Y1 and Y2 receptor mRNAs were elevated (12±2-fold and 90±47-fold, respectively, n=2) in diabetic vs. control tissue. Endothelium was removed and tail artery rings cut into 3-5 mm lengths. Isometric contractions were measured in response to 5 electrical stimuli (5 impulses, 1ms duration at 20Hz) delivered every 90 seconds. Specific NPY Y2 antagonist, BIIE0246 (100 nM), reduced diabetic responses by 29±8% (from 0.31±0.04 to 0.22±0.03 g, n=11, P<0.01) but did not change control responses. NPY Y2 receptor agonist, PYY_3-36 (10^-12–10^-7 M) had no direct vasoconstrictor affect on either tissue. Electrically evoked diabetic tissue responses were increased by 65±11% (from 0.36±0.11 to 0.44±0.1 g, n=3, P<0.05, paired Student’s t test) but were unaffected in controls. Specific NPY Y1 receptor antagonist BIBP3226 (1 μM) reduced responses in both diabetic and control tissue (diabetic: 39±9%; 0.36±0.06 to 0.22±0.05 g, n=6, P< 0.05; control: 36±18%, from 0.50±0.28 to 0.37±0.27 g, n=2, P< 0.05). There was no significant difference in this reduction between tissues (unpaired Student’s t test). These preliminary data indicate an increase in mRNA NPY Y1 and Y2 receptors in diabetic rat tail artery, evident functionally as an increased contribution from Y2 receptors in sympathetically evoked contraction.