A rapidly expanding body of evidence supports the concept that abnormalities of pathways of fibrin turnover and extravascular fibrin deposition contribute to the pathogenesis of acute lung injury (1). Concurrently increased intraalveolar coagulation and depressed fibrinolysis in the acutely injured lung favors formation of a transitional fibrin neomatrix, which undergoes organization and eventual fibrotic repair. This progression recapitulates that associated with wound healing (2). Morphologic observations suggest that remodeling of transitional fibrin contributes to alveolar fibrosis in chronic inffammatory lung diseases as well as in acute lung injury. In accelerated pulmonary fibrosis after acute lung injury and in the active phase of alveolitis associated with interstitial lung diseases, alveolar fibrin deposition is characteristic as it is in the early stages of acute respiratory distress syndrome (1). Similarly, in bleomycininduced lung injury, early fibrin deposition occurs during the initial phase of exudative alveolitis and persists as alveolar and interstitial fibrosis ensues (3). More recent studies of transgenic mice overexpressing or deficient in components of the fibrinolytic pathways further support a linkage between aberrant pulmonary fibrin turnover and subsequent fibrotic repair of the injured lung. Intraalveolar fibrin was blocked after hyperoxic challenge in mice deficient in plasminogen activator inhibitor-1 (4), suggesting that blockade of locally expressed plasminogen activators by this inhibitor plays a crucial role in alveolar fibrin clearance. Similarly, pulmonary fibrosis was likewise increased in bleomycin-treated mice overexpressing PAI-1 and fibrosis was decreased in PAI-1 deficient mice (5). These effects on histologic and biochemical indices of fibrosis were presumably attributable to modulation of the fibrinolytic activity and extent of transitional fibrin in the acutely injured lung. Günther and colleagues extend this work and used a novel aerosolization strategy to prevent pulmonary fibrosis in bleomycin-challenged rabbits (6). The authors chose to administer an anticoagulant, heparin, or a fibrinolysin, urokinase plasminogen activator, and show that both interventions protect the lungs against the development of pulmonary fibrosis. The key findings were that “early” therapy with aerosolized heparin, within days 2–12 days of bleomycin challenge, or “late” therapy with urokinase, days 14–24 post-bleomycin, most effectively attenuated the fibrotic response. A strength of this study is that the assessments of fibrosis are comprehensive and clinically germane, including normalization of lung compliance as well as consistent improvements in biochemical, radiographic and histologic analyses. The new wrinkle of this provocative study is that aerosolized delivery of either heparin or urokinase can attenuate the fibrotic response, suggesting that reversal of the increased procoagulant and depressed fibrinolytic responses in the alveolar compartment is responsible for the salutary effect. Günther and colleagues now show that either agent, when aerosolized, remains active in lavage ffuids from the injured lungs, in support of this concept. The findings build upon and validate previously published work patients with pulmonary tuberculosis. Am J Respir Crit Care Med