High-mobility group box 1 (HMGB1) is an endogenous alarm sensor against extracellular damage signals and initiates TLR (toll-like receptor) responses closely linked to angiogenesis through MyD88, its specific adaptor protein. Interest in regulation of HMGB1-TLR as a potential therapeutic approach is increasing but this regulatory effect in pathologic angiogenesis still remains unclear. Through a mouse model of laser coagulation-induced choroidal neovascularization (CNV) we confirmed that disturbing HMGB1 by its specific antibody and recombinant HMGB1 protein significantly reduces and induces CNV, respectively. To examine whether HMGB1 influences CNV through TLR signal, we then used MyD88 KO mice and the effects of HMGB1 antibody and recombinant protein on CNV completely blocked. Taken together, these data suggest that HMGB1 is a potential endogenous or exogenous regulator of pathophysiologic angiogenesis and MyD88 is an essential mediator for HMGB1-induced angiogenesis.