This study aimed to explore the protective effects of a Chinese herbal formula， Jinshui Huanxian formula (JHF)， on experimental pulmonary fibrosis and its underlying mechanisms. After being treated with single dose of bleomycin (5 mg/kg) intratracheally， rats were orally administered with JHF and pirfenidone from day 1 to 42， then sacrificed at 7， 14， 28， or 42 days post-bleomycin instillation. JHF ameliorated bleomycin-induced pathological changes， collagen deposition in the rat lung and recovered pulmonary function at different days post-bleomycin instillation. In lungs of JHF-treated rats， the levels of total superoxide dismutase， catalase and glutathione were higher， and myeloperoxidase and methane dicarboxylic aldehyde were lower than those in vehicle-treated rats， respectively. Additionally， JHF inhibited the expression of NADPH oxidase 4 (NOX4) and increased the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in lung tissues. ， JHF and ruscogenin， a compound of Ophiopogonis Radix contained in JHF， significantly inhibited transforming growth factor β1 (TGF-β1)-induced differentiation of fibroblasts. Furthermore， JHF markedly decreased the level of reactive oxygen species in TGF-β1-induced fibroblast. In line with this， upregulation of NAD(P)H: quinone oxidoreductase 1 and heme oxygenase 1， and downregulation of NOX4 were found in JHF-treated fibroblast induced by TGF-β1. While on the other hand， Nrf2 siRNA could suppress the JHF-mediated inhibition effect on alpha-smooth muscle actin (α-SMA)， and FN1 expression induced by TGF-β in fibroblasts. These results indicated that JHF performed remarkably therapeutic and long-term effects on pulmonary fibrosis in rat and suppressed the differentiation of fibroblast into myofibroblast through reducing the oxidative response by upregulating Nrf2 signaling. It might provide a new potential natural drug for the treatment of pulmonary fibrosis.