Objective To investigate the effects of quercetin on interstitial transformation, inflammation, and the NOX4-P62 signaling pathway in lung tissue of rats with pulmonary fibrosis to provide an experimental basis for further elucidating the mechanism of quercetin in pulmonary fibrosis. Methods Rats were divided into control, BLM and BLM+ QUE groups. The appearance of lung tissue in each group was observed on days 10, 20 and 30 after modeling. Pulmonary fibrosis was evaluated by HE staining. NOX4 and P62 in lung tissue, and α-SMA and E-cadherin in A549 cells were detected by western blotting. TGF-β1, IL-1β and TNF-α were measured by ELISA. Results Symptoms in the BLM+QUE group were milder than those in the BLM group on day 7, and significantly relieved on day 28. TGF-β1, IL-1β, TNF-α, NOX4 and P62 expression in the BLM+QUE group was lower than that in the BLM group on day 10 (P>0. 05), but it was much expression lower than that in the BLM group on days 14 and 28 (P<0. 05). Compared with the control group, E- cadherin and α-SMA expression in the TGF-β1 group was significantly decreased and increased, respectively (P<0. 05). Compared with the TGF-β1 group, E-cadherin and α-SMA expression in the TGF-β1 + QUE group were significantly increased and decreased, respectively ( P< 0. 05 ). Conclusions Quercetin inhibits TGF-β1. EMT of A549 cells alleviates the inflammatory reaction and pulmonary fibrosis induced by bleomycin in rats. Autophagy is inhibited by bleomycin-induced pulmonary fibrosis in rats. Quercetin inhibits the NOX4-P62 signaling pathway, activates autophagy, and reduces pulmonary fibrosis in rats.