Abstract：Objective：To observe the effect of Bufei Huanxian Decoction on follistatin-like protein 1 （FSTL1）， Syndecan-1 and pulmonary fibrosis indexes in the treatment of idiopathic pulmonary fibrosis （IPF）. Methods：A total of 93 IPF patients who visited the Respiratory Department Outpatient and Ward of the First Affiliated Hospital of Henan University of Chinese Medicine from January 1，2022 to January 31，2024 were selected and randomly divided into the control group，the Bufei Huanxian Decoction group，and the combination group using a random number table method， with 31 patients in each group. The control group received oral treatment with Nintedanib， the Bufei Huanxian Decoction group received oral treatment with Bufei Huanxian Decoction，and the combination group received treatment with Bufei Huanxian Decoction combined with Nintedanib. After 12 weeks of treatment，three groups of lung function indexes before and after treatment were compared， including maximum vital capacity （VCmax）， total lung capacity （TLC）， and diffusion capacity of carbon monoxide （DLCO）， 6-minute walk test （6MWT）， St. George's Respiratory Questionnaire （SGRQ），serum Krebs von den Lungen-6 （KL-6），FSTL1，and Syndecan-1，as well as pulmonary fibrosis indicators such as lamin （LN），hyaluronic acid （HA），and type Ⅲ procollagen （PCⅢ）. Results： After treatment，the levels of VCmax，TLC，and DLCO in the combination group were increased when compared with those before treatment（ P＜0.05），and the levels of the three lung function indexes were higher than those in the control group and the Bufei Huanxian Decoction group （P＜0.05）；there was no significant difference in the levels of three lung function indexes before and after treatment between the control group and the Bufei Huanxian Decoction group （P＞ 0.05）. After treatment， the 6MWT in the combination group was increased when compared with that before treatment （P＜0.05），and the SGRQ score was decreased when compared with that before treatment （P＜0.05）；the improvement of both indicators was better than that in the control group and the Bufei Huanxian Decoction group （P＜ 0.05）. There was no significant difference in the 6MWT and SGRQ scores before and after treatment between the control group and the Bufei Huanxian Decoction group （P＞0.05）. After treatment， the levels of KL-6， FSTL-1， and Syndecan-1 in the combination group were decreased when compared with those before treatment （P＜0.05），and the levels of three indexes were lower than those in the control group and the Bufei Huanxian Decoction group （P＜0.05）； there was no significant difference in the levels of KL-6，FSTL-1，and Syndecan-1 before and after treatment between the control group and the Bufei Huanxian Decoction group （P＞0.05）. After treatment，the levels of LN，HA，and PC Ⅲ in all the three groups were decreased when compared with those before treatment （P＜0.05），and the levels of the three pulmonary fibrosis indexes in the combination group were lower than those in the control group and the Bufei Huanxian Decoction group （P＜0.05）； there was no significant differences in the three pulmonary fibrosis indicators between the control group and the Bufei Huanxian Decoction group （P＞0.05）. Conclusion：The combination of Bufei Huanxian Decoction and Nintedanib can better delay vassular endothelial injury in patients with IPF， improve pulmonary diffusion function，enhance exercise tolerance and quality of life，and to some extent delay the progression of IPF.