|Aqueous extraction of Citrus unshiu peels (AECUP) is mainly comprised with pro-angiogenichesperidin and narirutin. In this study, we report approaches to increasing the yields of extracted hesperidin and narirutinfrom Citrus unshiu peels using proper solvents. Significantly improved yields of both compounds were obtained using methanol and dimethyl sulfoxide (DMSO) compared to acetonitrile, ethyl acetate, ethanol, and isopropyl alcohol. Especially, effect of DMSO was by far the better of the two solvents in extraction of hesperidin. In addition, the DMSO extracted hesperidin significantly induced the pro-angiogenic effects of human umbilical vein endothelial cells (HUVECs) and markedly up-regulated phosphorylation of the ERK1/2 signaling pathway. These results demonstrate that pro-angiogenic inducer; hesperidin and narirutin can be simply, easily, and effectively extracted from Citrus unshiu peels.