Idiopathic pulmonary fibrosis (IPF) is one of the most frequent interstitial lung diseases (ILD) and a chronic progressive and fatal lung disease of unknown etiology. For the last two decades it is markedly improved the knowledge about underlying mechanisms of pulmonary fibrosis and helped to identify potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. On the other hand, NQO-1 is a homodimeric enzyme catalyzing the oxidation of NAD(P)H to NAD(P)+ by various quinones and thereby elevates intracellular NAD+. By using NAD+ as a cofactor, Sirt1 and Sirt3 cause the deacetylation of p65 in nuclei and p53 in mitochondria, respectively. In current study we examined the role of NQO-1 activation and its downstream signaling on bleomycin-induced lung fibrosis. C57BL/6 mice were treated with single intratracheal instillation of bleomycin. Mice were orally administered with compound X1, a NQO-1 activator, from 3 days before bleomycin exposure to 3 weeks after exposure. NQO-1 activation by compound X1 effectively attenuated bleomycin-in-duced inflammatory and fibrotic responses in lung tissue and BAL fluid analysis. We will discuss the protective role of NQO-1 on bleomycin-induced lung fibrosis by molecular biological and histological analyses. This work was supported by the National Research Foundation of Korea [NRF] grant funded by the Korea government [MEST] [No. 2012R1A1A2043961].