Lichens have been used in folk medicine for centuries and are symbiotic organisms of fungi and algae that produce unique secondary metabolites. Olivetoric acid is one of these secondary metabolites. In the present studs the effect of olivetoric acid isolated from acetone extract of the lichen Pseudevernia futfuracea (var. ceratea) on angiogenesis was evaluated. It displayed potent anti-angiogenic activities in vitro: inhibited proliferation of rat adipose tissue endothelial cells (RATECs) and disrupted endothelial tube formation in a dose-dependent manner. Furthermore, dose-dependent depolymerization effects of olivetoric acid on F-actin stress fibers were observed. Decrease in the tube formation of RATECs by olivetoric acid might be explained by a disorganization of the actin cytoskeleton. These findings suggest that olivetoric acid is a new anti-angiogenic agent and can be developed as a new therapeutic agent for angiogenesis-related diseases. Copyright (C) 2009 John Wiley & Sons, Ltd.