Although it is well known that endothelial function is compromised by ageing, less is known about the contribution of adipokines and/or myokines in the process of ageing. Irisin is an exercise-induced myokine1 that is implicated in the metabolic disturbances such as diabetes and obesity. Recently it has been shown that serum irisin levels significantly decrease in response to ageing2. Thus, the aim of the present study is to evaluate whether irisin is involved in vascular dysfunction normally observed with ageing and to identify if presence of PVAT alters responses of irisin in aged rats. Ethical approval was taken from the Marmara University Animal Ethics Committee. Female Sprague-Dawley rats were obtained; 3-month-old, (young; n=10) and 18-month-old, (aged, n=10) groups. Blood was collected for the biochemical measurements. Visceral adipose tissue was weighed to measure the body fat ratio (BFR). Cardiac and aortic samples were taken to histopathological examination. Aortas were taken for wire myography studies in the absence or presence of PVAT (PVAT− and PVAT+ rings). One-way analysis of variance followed by Tukey’s post hoc test and unpaired Student’s t-test were performed with statistical significance set at p<0.05. Ageing caused a significant increase in plaque area of aortas and increased hypertrophic area in cardiac tissues, BFR, hypertrophy index (Heart Weigth/BW), serum cholesterol, glucose, TNF-α, cardiac malondialdehyde and myeloperoxidase levels compared to young group (p<0.01-p<0.05). Ageing caused significant reductions in tissue levels of glutathione, superoxide dismutase and catalase (p<0.001). Additionally, irisin levels found to be decreased in the aged group in both PVAT and plasma compared to young group (p<0.01). Ageing decreased the contractility responses to phenylephrine and relaxation responses to carbachol (CCh) in PVAT− and PVAT+ rings (p<0.05). However, presence of PVAT positively improved CCh responses compared to PVAT-. Irisin in the organ bath caused a dose-dependent relaxation of aortic rings in both young and aged groups. Irisin-induced relaxations were significantly impaired in the aged group compared to the young (p<0.05). Irisin responses were significantly reduced in both groups following addition of nitric oxide (NO) inhibitor L-NG-Nitroarginine methyl ester (L-NAME; 10-4M) into the organ bath. Our results indicate that ageing is associated with chronic systemic inflammatory changes and vascular dysfunction. Irisin directly causes vasorelaxation even in the absence of PVAT. Irisin- induced relaxation of aorta is partially NO dependent in both young and aged animals. Reduced responsiveness to irisin-induced relaxation seems to be an ageing phenotype. These results reveal previously uncharacterized role of irisin and PVAT in ageing.