Idiopathic pulmonary fibrosis is regarded as a lethal chronic disease accompanied with excessive collagen disposition. In the early stage, monocyte chemotactic protein-1 (MCP-1) plays a crucial role in the process. Our previously screening with a vitro assay through inhibition of chemotaxis of RAW264.7 cells stimulated by MCP-1 proved that several analogues of thiazolidinediones, especially (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (SKLB010), had potency of protecting acute liver injury in vivo without obvious toxicity. The present study aimed to investigate the preventive effect of SKLB010 in bleomycin-induced pulmonary fibrosis and further explore the underlying mechanisms. Bleomycin (BLM) was injected intratracheally at a single dose of 5 U kg(-1) for pulmonary fibrosis induction. SKLB010 (25, 50 mg/kg/d) was respectively administrated by gavages 1 d prior to BLM administration and continued to the end of the study (for 4 weeks). Our results demonstrated that SKLB010 diminished the increase of macrophage, neutrophil and lymphocyte counts as well as the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in bronchoalveolar lavage fluid on day 14 (p<0.05). Moreover, oral gavages of SKLB010 also ameliorated histological changes and significantly suppressed collagen deposition on day 28. The treatment with SKLB010 exerted approximately 34.6% the hydroxyproline content reduction for 25 mg/kg dose and 56.7% reduction for 50 mg/kg dose in contrast to bleomycin-induced group (p<0.05). Meanwhile, SKLB010 inhibited the overexpression of tumor growth factor (TGF)-β1 and Smad3 in a dose-dependent manner. In conclusion, our results showed that SKLB010 could attenuate the BLM-induced pulmonary fibrosis in vivo and therefore be a promising anti-fibrogenic candidate.