【Abstract】Objective To investigate the protective effect and mechanism of Salvia miltiorrhiza (SM) combined with ligustrazine on pulmonary fibrosis in rats. Methods 180 healthy male rats were selected as subjects and randomly divided into group A, group B, group C, group D, group E and group F, according to their treatment. Each group of rats were treated with 0.9% sodium chloride solution for tracheal perfusion, and the other four groups were treated with bleomycin tracheal perfusion to establish pulmonary fibrosis model. After that, the rats in group A and group B were treated with 0.9% sodium chloride solution daily. Group C was treated with dexamethasone. Group D was treated with salvia miltiorrhiza and ligustrazine combined with low dose. Group E was treated with salvia miltiorrhiza combined with ligustrazine. Group F was treated with salvia miltiorrhiza combined with high dose of ligustrazine. The expression levels of serum transforming growth factor beta 1 (TGFbeta 1), lung tissue, connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), hydroxyproline (HYP), protein tyrosine kinase in lung tissue(JAK1), signal transducer and activator of transcription 1 (STAT1), 1 collagen (Col I) and collagen type III (Col III) mRNA, intercellular adhesion molecule-1 (ICAM-1), serum tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-17 among 4 groups of rats were compared between different time points after treatment. Results The levels of TGFβ1, TNF-α, CTGF, bFGF, JAK1, STAT1 and ICAM1 in group C, D, E and F were significantly higher than those in group B at the 7th, 14th and 28th day of treatment. No significant difference was detected between group B and group D, group E and group F (P<0.05).The levels of IL-6, IL-17, HYP, MDA, SOD, ColⅠmRNA and ColⅢmRNA in group C, D, E and F were increased or decreased than group A compared with group B at the 7th, 14th and 28th day of treatment. The increasing or decreasing level of group E and group F was greater than that of group B and group D. No significant difference was detected between group B and group D, group E and group F (P<0.05). The levels of alveolar inflammation and pulmonary fibrosis in C, D, E and F groups were lower than those in group A compared with group B at the 7th, 14th and 28th day of treatment. The decreasing level of group E and group F was higher than that of group B and group D. No significant difference was detected between group B and group D, group E and group F, and the level of alveolar inflammation and pulmonary fibrosis decreased gradually with the prolongation of time (P<0.05). Conclusion Different doses of danshen combined with ligustrazine has a protective effect on rat pulmonary fibrosis of the lung tissue and the main mechanism for Salvia Ligustrazine can inhibit lung TGF beta 1, TNFalpha, a closed expression of Col 1 mRNA and Col of mRNA and other cytokines.