Vascular dysfunction is a common consequence of diabetes mellitus. Alterations in sensitivity/responsiveness to neurotransmitters (noradrenaline (NA), ATP and NPY) may underlie functional abnormalities of diabetic blood vessels (Speirs et al., 2006). Previous studies have reported considerable variation in such alterations, potentially due to sampling at different time-points after induction of diabetes. In this study, contributions of NPY Y₁ and NPY Y₂ receptors to sympathetic vasoconstriction were explored in tail artery of diabetic rats at 20 and 40 weeks of age. Tail arteries were excised from diabetic (60 mg.kg-1 streptozotocin, i.p. injection at 8 weeks) and control Sprague-Dawley rats at 20 and 40 weeks of age. Receptor expression was determined at mRNA level using RT-PCR (normalized to β-actin). Isometric contractions were recorded from proximal sections (3-5 mm, endothelium-denuded) in response to electrical stimuli (5 impulses, 1ms duration at 20Hz) delivered every 90 seconds. NPY (100nM) potentiated responses in all groups (20 week control vs diabetic: 39 ± 10%, mean ± S.E., n=8; vs 62±11%, n=6; 40 week control vs diabetic: 56±4%, n=8 vs 69±8%, n=5; P<0.01 in each case, unpaired Student’s t-test). No differences were detected between time-points. NPY Y₁ specific antagonist BIBP3226 (1μM) reduced responses in all groups (20 week control vs diabetic: 40±7% vs 37±6%, n=8 and P<0.01 in each case; 40 week control vs diabetic: 32±3 % vs 26±3%, n=5 and P<0.05 in each case). No differences were detected between groups. NPY Y₂ agonist PYY_3-36 potentiated responses in 20 week old diabetic artery (P<0.01, 42±5%, n=9) relative to control (1±2%, n=5). However, this effect was not observed in 40 week old diabetic artery (12±3%, n=5) relative to control (4±%, n=5). NPY Y₂ specific antagonist BIIE0246 significantly reduced responses in 20 week old diabetic artery (P<0.01, 32±6.10%, n=9) relative to control (3.4±6.25%, n=8). Similar to Y₂ agonist, this was not apparent in 40 week old diabetic artery (5±1%, n=5) relative to control (3±1%, n=5). NPY Y₁ receptor expression increased (P<0.05; 3.63±0.07, n=5) in diabetic arteries at 20 weeks relative control (1.28±0.06, n=5). However, no change in NPY Y₁ receptor expression (1.19±0.02, n=6) was observed in diabetic artery at 40 weeks relative to control (0.82±0.06, n=5). NPY Y₂ receptor expression was elevated in 20 week old diabetic artery (P<0.01, 3.38±0.1, n=5) relative to control (1.22±0.04, n=5). In contrast, there was a reduction in expression (P<0.05, 0.36±0.02, n=5) in 40 week old diabetic artery relative to its control (1.09±0.01, n=5). These data indicate that enhanced NPY Y₁ and Y₂ receptor expression and its associated contribution to vasoconstriction in a model of Type 1 diabetes has a temporal aspect to its involvement in peripheral vascular dysfunction.