Background: Perivascular adipose tissue (PVAT) reduces vascular tone in isolated arteries in vitro, however there are no studies of PVAT effects on vascular tone in vivo. In vitro adipocyte beta(3)-adrenoceptors play a role in PVAT function via secretion of the vasodilator adiponectin. Objective: We have investigated the effects of PVAT on vessel diameter in vivo, and the contributions of beta(3)-adrenoceptors and adiponectin. Method: In anaesthetised rats, sections of the intact mesenteric bed were visualised and the diameter of arteries was recorded. Arteries were stimulated with electrical field stimulation (EFS), noradrenaline (NA), arginine-vasopressin (AVP), and acetylcholine (Ach). Results: We report that in vivo, stimulation of PVAT with EFS, NA, and AVP evokes a local anti-constrictive effect on the artery, whilst PVAT exerts a pro-contractile effect on arteries subjected to Ach. The anti-constrictive effect of PVAT stimulated with EFS and NA was significantly reduced using beta(3)-adrenoceptor inhibition, and activation of beta(3)-adrenoceptors potentiated the anti-constrictive effect of vessels stimulated with EFS, NA, and AVP. The beta(3)-adrenoceptor agonist had no effect on mesenteric arteries with PVAT removed. A blocking peptide for adiponectin receptor 1 polyclonal antibody reduced the PVAT anti-constrictive effect in arteries stimulated with EFS and NA, indicating that adiponectin may be the anti-constrictive factor released upon beta(3)-adrenoceptor activation. Conclusions: These results clearly demonstrate that PVAT plays a paracrine role in regulating local vascular tone in vivo, and therefore may contribute to the modulation of blood pressure. This effect is mediated via adipocyte beta(3)-adrenoceptors, which may trigger release of the vasodilator adiponectin