Inorganic polyphosphate(polyP)is wide spread in biology and exhibits striking procoagulant ef-fects in vivo.Long-chain polyphosphate(such as those present in infectious microorganisms)is a potent,natural patho-physiologic activator of the contact pathway of blood clotting and promotes thrombosis and inflammation,which suggest that antagonizing polyP function in vivo may be an attractive approach for identifying novel antithrombotic agents,perhaps with reduced bleeding side effects compared with conventional anticoagulant drugs.Short-chain polyphosphate(secreted from activated human platelets)remarkably accelerates factor V activation,absolutely abrogates the anticoagulant function of tissue factor pathway inhibitor,increase fibrin clot structure,and accelerates factor XI activation by thrombin.So polyP may be used as hemostatic agent.In this paper,the procoagulant role of polyP and the mechanism underlying polyP modu-lates blood clotting and the strategy of screening polyP inhibitors are described in detail.