Cold-induced vasodilatation was first described by Lewis (1930) and remains an important phenomenon in protecting against cold-induced injury. Although this field of research has been extensively studied, the mechanisms involved in cold-induced vasodilatation currently remains unclear. The non-selective cation channel, transient receptor potential ankyrin 1 (TRPA1) is expressed in a subset of sensory neurons and was initially reported to sense noxious cold temperature. Although several studies have previously investigated its role as a cold sensor in the study of pain, its influence in cold-induced vascular responses is unknown. We have investigated the influence on peripheral vascular responses to environmental cold exposure in skin in vivo. Using non-invasive laser Doppler flowmeter techniques, peripheral blood flow was measured in anaesthetised mice before (5-10 min:baseline) and after local cold exposure of the mice hindpaw (30 min). Results were analysed as area under the response curve (AUC), expressed as mean + S.E.M. in arbitrary flux units (x1000 flux units) and analysed by 2-way ANOVA + Bonferroni’s test. Cold treatment caused the expected reduction in skin blood flow, followed by a dilator response that was monitored for the following 30 min in WT mice. This response was substantially reduced in TRPA1 KO mice compared to respective age-matched WT mice (245.1 + 39.6 vs 86.1 + 11.0, x 1000 flux units, AUC, n=6, p<0.01) and antagonised by the TRPA1 antagonist HC030031 (100mg/kg, i.p., n=5, p<0.001). The cold-induced response was also shown to be significantly reduced in WT mice pre-treated with the calcitonin gene related peptide (CGRP) receptor antagonist, CGRP8-37 (400nmol/kg, i.v., n=7, p<0.001) and the substance P neurokinin-1 receptor antagonist SR140333 (480nmol/kg, i.v. n=5, p<0.001), suggesting a prominent role of neuropeptides in the cold-induced vascular responses. These results provide novel evidence of a major involvement of TRPA1 in local cold-induced vascular responses in vivo, with findings indicating a role for TRPA1-dependent neurogenic vasodilation as a key component of this response.