Vascular dysfunction is a common consequence of diabetes mellitus. Alterations in sensitivity and/or responsiveness to the ‘sympathetic triad’ of neurotransmitters (noradrenaline, ATP and NPY) may underlie functional abnormalities of diabetic blood vessels (Chow et al., 2001; Tefamariam, 1995). Recently, we have found a greater contribution to vasoconstriction from NPY Y₁ and Y₂ receptor subtypes in arteries from diabetic rats (Kerlin et al., 2006). In this study we have further investigated alterations in expression of NPY receptor subtypes and their associated functional responses in diabetic rat tail arteries. Diabetes was induced in Sprague-Dawley rats (8 weeks old) by injection of streptozotocin (i.p., 60 mg.kg^-1). Tail artery was excised from humanely dispatched rats at 20 weeks. Receptor expression was determined at both mRNA and protein level using RT-PCR (normalized to GAPDH mRNA) and Western blotting (standardized to β-actin) respectively. Sections of proximal tail artery (3-5 mm, endothelium-denuded) were suspended in tissue baths perfused with Krebs-Hansleit solution for isometric contractile studies. NPY Y₁ and NPY Y₂ mRNA receptor expression was significantly increased, 2.84 ± 0.47 fold (n=5, P<0.05; unpaired Student’s t-test) and 2.78 ± 0.55 fold (n=5, P<0.01), respectively, in diabetic rat tail artery relative to the age-matched control. Parallel increases in NPY Y₁ (n=5, P<0.05, 5.76 fold) and NPY Y₂ (n=5, P<0.01, 1.73 fold) receptor expression were observed at protein level. A 5.45 ± 0.21 fold decrease in NPY Y₅ receptor mRNA expression (n=5, P<0.01) was detected in diabetic rat tail artery relative to the control. No change was observed in sympathetically-evoked constrictions (20 impulses at 20 Hz, pulse duration 1 ms, supra-maximal voltage) from control and diabetic tail artery upon the application (5 nM) of the NPY Y₅ antagonist CGP71683. We have now confirmed at protein level, in addition to mRNA level, an increase in expression of NPY Y₁, and Y₂ receptors in diabetic rat tail arteries, which may explain their increased contribution to vasoconstriction seen previously (Kerlin et al., 2006). Our on-going studies have shown that NPY Y₅ receptors are not involved in vasoconstriction in control or diabetic tissues, although NPY Y₅ mRNA is down-regulated in diabetes. Therefore, of these changes, only the increase in NPY Y₁ and NPY Y₂ expression are of consequence for contraction.