We used optical imaging of live animals and transgenic technology to develop a pulmonary fibrosis model in mice that can non-invasively and in real-time trace the pulmonary fibrosis process. Fibroblast activation protein-alpha (FAP alpha) is selectively expressed in fibrotic foci of human pulmonary fibrosis. It is not expressed in normal tissue. We confirmed that FAP alpha is upregulated in fibroblasts of murine pulmonary fibrosis. Moreover, TGF-beta 1, a central pathological mediator of fibrotic diseases, could promote FAP alpha expression in mouse embryonic fibroblasts. Luciferase reporter assays showed that 5.4 kb FAP alpha promoter response activities to TGF-beta 1 was stronger than of the 2.1 kb promoter. We generated a transgenic mouse line expressing firefly luciferase under the control of the 5.4 kb FAP alpha gene promoter (FAP alpha-p-luc). After experimentally inducing murine pulmonary fibrosis, there luminescence appeared in the chests and excised lungs of FAP alpha-p-luc mice. The intensity of luminescence became stronger with the exacerbation of pulmonary fibrosis. Fluorescence intensity reflects the degree of pulmonary fibrosis in FAP alpha-p-luc mice. and this mouse model may be used to investigate molecular mechanisms and drug screening of pulmonary fibrosis.