Angiogenesis, the formation of new blood capillaries from existing vessels, is required for physiological processes such as embryonic development, wound healing, and female reproduction, but when dysregulated can contribute to tumour growth and atherosclerosis. Endothelial cell migration and proliferation, in response to angiogenic stimuli, such as hypoxia, plays an essential role in this process. Here, we examine the effect of the novel, cysteine-rich secretory protein, resistin, on the angiogenic responses of murine b.End.5 endothelioma cells. Resistin causes insulin resistance in hepatic and peripheral murine tissues, is present within human and murine atherosclerotic lesions, and induces inflammatory, proliferative and angiogenic responses in vascular cells. Using a model in which endothelial cells remodel an induced ‘wound’ in a confluent cell monolayer, we show that treatment with murine recombinant resistin (50ng/ml) increases growth and migration of endothelial cells by 59% and 33% (p<0.001) over 24 and 48h, respectively, compared with the control incubation. Under hypoxic conditions murine resistin and VEGF stimulated comparable degrees of growth and migration, possibly via the same pathway as no additive response was noted when both resistin and VEGF were added together. These effects of resistin were accompanied by an apparent increase in network formation, on a MatrigelTM substrate. Resistin induces a significant degree of endothelial cell migration, as judged by apical to basolateral migration (5h) across TransWell culture dishes (8μm pore), and in response to treatment in the presence or absence of murine resistin (50ng/ml), VEGF (10ng/ml) or both resistin and VEGF. Resistin and VEGF increased endothelial cell migration by 48% and 23%, respectively, (p<0.01), compared with the control incubation; cellular migration increased by 66% (p<0.01) in the presence of both resistin and VEGF. Finally, the presence of resistin (30-100ng/ml) also induced a mild proliferative effect (14-15%; p<0.05) in b.End.5 cells, as judged by conversion of MTT to formazan. These data suggest that resistin may promote angiogenesis by increasing endothelial cell proliferation and migration, and may have an important role in pathological processes such as atherosclerosis.