We evaluated fibrinolytic therapy with bolus injections of sctPA and scuPA alone and with DSP added during late-stage, chronic empyema in rabbits to (i) further validate a rabbit model of S. pneumoniae induced empyema [42], (ii) determine the MED of human sctPA and scuPA for this rabbit model of late-stage or chronic empyema, and (iii) demonstrate that DSP-based PAI-1-TFT increases the efficacy of plasminogen activators in a model of chronic, late-stage empyema in a manner similar to that observed in rabbit models of chemically induced pleural injury and acute empyema [41]. The gene discussed is SERPINE1; the disease is empyema.