Abstract: The present invention features pharmaceutical compositions and methods to inhibit angiogenesis, with implications to cancer therapy. These methods are based on the discovery that activated thrombin has antiangiogenic activity and that this antiangiogenic activity is at least in part, mediated through the activation of a class of thrombin receptors termed, Protease Activated Receptor (PAR). Pharmaceutical compositions and methods are also directed to a class of proteases which mediate this activation, particularly the urokinase plasminogen activator (uPA) polypeptide.