Lung fibrosis is characterized by excessive accumulation of extracellular matrix components leading to progressive airflow limitation. Distinct pro-fibrotic pathways converge on the activation of transforming growth factor beta (TGF-), a central growth factor implicated in most fibroproliferative diseases. Recently, enforced expression of bioactive hTGF-1 in lungs of transgenic mice was shown to recapitulate several key pathophysiologies observed in fibrotic disorders of the lung including cellular inflammation, tissue fibrosis, and myofibroblast hyperplasia. Inducible expression of hTGF-1 in this system provided us with a unique opportunity to characterize TGF- driven mechanisms that precede and/or follow the onset of inflammation and fibrosis. Using gene expression profiling in lungs, we demonstrate temporal activation of key genetic programs regulating cell movement and invasiveness, inflammation, organ remodelling and fibrosis. Consistent with our gene expression data, multiple soluble mediators associated with inflammation and tissue remodelling were markedly elevated in the bronchoalveolar lavage fluid of mice expressing hTGF-1. Interestingly, we observe significant TGF-1-driven infiltration of F4/80+ mononuclear cells producing bioactive arginase, a marker of alternatively activated macrophages. Finally, we identified a common "fibrosis" gene signature when comparing our findings to published data derived from both preclinical and clinical studies.