Eleven known prenyl xanthones, isolated from the pericarp of Garcinia mangostana, were tested for their ability to inhibit the phosphorylation of kinase domain receptor (KDR) tyrosine kinase. α-Mangostin was found to inhibit phosphorylation of KDR. α-Mangostin also showed to inhibit phosphorylation of the Y1175 residue of KDR (10 μM). This is the first report that α-mangostin inhibited the phosphorylation of KDR tyrosine kinase and also the Y1175 residue of KDR. α-Mangostin also showed inhibitory effects on proliferation of human umbilical vein endothelial cells (HUVECs) (IC(50) 1.2 μM) and human umbilical artery endothelial cells (IC(50) 2.4 μM), as well as the migration (IC(50) 0.034 μM) and tubule formation (at the concentrations of 0.6 and 1.2 μM) of HUVECs. These results suggest that the inhibition of the phosphorylation of KDR tyrosine kinase is concerned in the anti-angiogenic activity of α-mangostin.