Recent studies suggest that the plasmin system plays an active role in tissue remodeling. Plasmin degrades the extracellular matrix (ECM), either directly removing glycoproteins from ECM or by activating matrix metalloproteinases (MMPs). PAI-1 blocking MMPs may prevent ECM degradation, but inhibiting fibrinolysis leads to fibrin accumulation and fibrosis. Components of the plasmin system including tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and plasminogen activator inhibitors PAI-1 and PAI-2 are synthesised by airway cells, and inflammatory mediators affect their expression. The plasmin system, in turn, actively influences the production of inflammatory mediators and growth factors, extending pathological structural changes in the airway. Modulation of the plasmin system might be a new pharmacological strategy that could inhibit the development of airway remodeling.