<p>This study was aimed to evaluate the chemical composition of ethanolic leaf extract of a marine macro-alga <em>Sargassum wightii</em> (ELESW) followed by its vascular endothelial growth factor (VEGF) induced anti-angiogenic effect against human umbilical vein endothelial cells (HUVECs). The effect of ELESW on cell viability and its potential against <em>in vivo</em> angiogenesis was assessed by using the MTT and CAM assay respectively. The phenolic, flavonoid, polysaccharides, and protein content of ELESW were found to be 56.0 ± 4.1 mg GAE/g, 26.3 ± 3.6 mg QE/g, 284.2 ± 6.2 μg/mL, 100.9 ± 8.9 μg/mL, respectively. In angiogenesis, ELESW (100, 500 and 1,000 μg/mL) significantly inhibited VEGF induced angiogenesis as well as VEGF-induced proliferation and tube formation of HUVECs in a dose-dependent manner. Upon stimuli-tion by VEGF, HUVECs rapidly increased reactive oxygen species production, which was significantly blocked by treatment with ELESW. These findings suggesting that <em>S. wightii</em> could be a valuable candidate of therapeutic efficacy.</p>
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