Angiogenesis is an essential step in tumor progress and metastasis. Accordingly, small molecules that inhibit angiogenesis would appear to be a promising way to cure angiogenesis-related diseases, including cancer. In the present study, we report that streptochlorin, a small molecule from marine actinomycete, exhibits a potent antiangiogenic activity. The compound potently inhibited endothelial cell invasion and tube formation stimulated with vascular endothelial cell growth factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to the cells. In addition, streptochlorin inhibited TNF-${alpha}$-induced $NF-{kappa}B$ activation in the newly developed cell-based reporter gene assay. These data demonstrate that streptochlorin is a new inhibitor of $NF-{kappa}B$ activation and can be a basis for the development of novel anti-angiogenic agents.