The anti-angiogenic activity of resveratrol, a stilbenoid found in grapes and peanuts was assessed using zebrafish model. Zebrafish embryos at 50% epiboly stage [5.25 hours post fertilization (hpf)] were treated with (10, 50 and 100μM) resveratrol to evaluate their effects on angiogenesis and also the toxicity effects. Morphological variations including angiogenic phenotypes, hatching, survival and heart rates were examined. The number of apoptotic cells during embryonic development was evaluated using acridine orange staining. Angiogenesis was measured by scoring the development of intersegmental vessel (ISV). Role of vascular endothelial growth factor VEGF and its receptor VEGFR2 was evaluated by studying their gene expression using Reverse Transcriptase PCR. Resveratrol at 100μM could inhibit the formation of major blood vessels (ISVs) possibly by downregulating VEGF and its receptor VEGFR2. The toxicity assays revealed various morphological deformities including developmental delay, pericardial edema and tail bending, reduction in survival and hatching rates in embryos treated with different concentrations of resveratrol in a dose dependent manner. The downregulation of VEGF and its receptor VEGFR2, which are the primary determinants of growth and blood vessel formation suggest that resveratrol of micromolar (μM) concentration might potentiate its anti-angiogenic activity by targeting genes involved along the VEGF signaling pathway. This study, for the first time, identifies resveratrol to possess anti-angiogenic activity in vivo and suggests that it might have a great potential for future research and development as a therapeutic agent.