We have studied how fibrinolytic activity is expressed both in plasma and on vascular endothelial cells (VECs) under physiological and pathological conditions. The activation of coagulation cascade and the resulted fibrin formation is an important trigger to express high fibrinolytic activity in plasma. Binding of tissue plasminogen activator (tPA) and Glu-plasminogen (Glu-plg) on fibrin surface, and the resulted tri-molecular complex formation and the confomational change of Gluplg are the most important underlying mechanisms. We have analyzed those mechanisms and recently demonstrated using real-time imaging technique (Suzuki Y et al, Blood, 2011, Brzoska T et al, PLoSONE 2015). We have also proposed that the activated coagulation factors enhance tPA activity by neutralizing the activity of plasminogen activator inhibitor type 1 (PAI-1) (Urano T et al, JTH 2003;1:2615-2620, Iwaki T et al, JTH 2011;9:1200-1206). We recently focused on how fi brinolytic potential is highly maintained and its activity is effectively expressed on the surface of VECs.