We have investigated a potential anti-angiogenic effect of plaunotol, an extract from the leaves of Plau-noi, in an angiogenesis model consisting of human umbilical vein endothelial cells (HUVECs). Plaunotol inhibited the proliferative activity of HUVECs in a dose-dependent manner. In addition, it caused a remarkable decrease of the ability of HUVECs to adhere and spread on gelatin and vitronectin, but not fibronectin. Tube-like formation in Matrigel was also inhibited in a dose-dependent way. These results strongly suggest the specific inhibition of integrin alphavbeta3 to be the main event of plaunotol-induced suppression of angiogenesis. The alphavbeta3 antagonists are known to be potent inhibitors of tumor angiogenesis and plaunotol, by causing the functional inhibition of alphavbeta3, should be considered a promising new anti-angiogenic drug.