Background: Pulmonary fibrosis is a condition characterized by dysregulated tissue repair and remodeling leading to lung tissue scarring. Here, we tested the antifibrotic effect of OTR4120 in a bleomycin-induced mouse model of pulmonary fibrosis. Methods: Swiss mice were randomly divided into four experimental groups: saline-treated control group, OTR4120 group, bleomycin-induced fibrosis groups with and without OTR4120. Lungs were compared using the lung/body weight index, and the interstitial injury area extent was graded using histopathological assessment of haematoxylin and eosin-stained lung tissue sections. Lung tissue Collagen I and Collagen III levels, and blood cytokine levels were measured using a Collagen colorimetric kit and a Cytokine colorimetric kit, respectively. Results: The clinical signs in all animals resolved gradually on day 17 after Bleomycin injections and 6 days after OTR4120 treatment, and disappeared almost completely at days 24 after Bleomycin injections and days 13 after OTR4120 treatment. Lung/body weight index values were significantly lower in the bleomycin-OTR4120 treated group versus the bleomycin only group (respectively 7.31; 9.97 and 7.63 mg/g, p<0.01). Histopathological analyses suggest that OTR4120 treatment ameliorated the increased inflammatory cell infiltration, and attenuated the interstitial thickening, associated with bleomycin-induced fibrosis. Collagen III and cytokine levels were decreased in the OTR4120 group versus the fibrotic (bleomycin only) group. OTR4120-treated animals were less affected in their behavior, did not loose weight nor appetite, and recovered overall activities within 6 days of OTR4120 treatment, while none of the vehicle-treated animals recovered to normal. Conclusion: OTR4120 is a potential candidate to reduce lung fibrosis