The AMP activated protein kinase (AMPK) is expressed in both endothelium and vascular smooth muscle of large as well as small arteries- It is involved in control of vascular tone and angiogenesis. AMPK stimulators exert vasodilation in microvessels in vivo and in vitro. This action of AMPK seems to be mainly due to direct effects on vascular smooth muscle. The dilator actions of AMPK stimulation seem to affect multiple pathways the functional significance of each may depend on differential expression of the hetrotrimeric enzyme in different species and / or vascular regions. Vasodilation is exerted either by a decrease of intracellular free calcium concentration in smooth muscle and / or by a decrease of calcium sensitivity of its contractile apparatus. The decrease of the calcium concentration as observed in microvessels has been shown to be due to activation of potassium channels in vascular smooth muscle. The decrease of calcium sensitivity as observed in large vessels has been attributed to a phosphorylation of myosin light chain kinase thereby decreasing its activity but own experiments point towards actions of AMPK on.myosin light chain phosphatase in microvessels. The smooth muscle effects of AMPK have mainly been shown by using the pharmacologic stimulator of AMPK, A769662, but the antidiabetic, AMPK stimulating, metformin seems to activate the same signaling pathways. In vitro, similar effects can be induced by exposure of the vessels to deoxyglucose suggesting that AMPK may play an important role in the response of vascular smooth muscle to hypoxia. The observations in isolated cells that AMPK can be further activated in a calcium dependent manner and by alterations of the cellular redox state suggest that the potent vasomotor actions of AMPK may play a significant role in physiologic control of vascular tone as well as in a number of pathophysiologic conditions. Supported by 7FP EU integrated Network \