Abstract: OBJECTIVE To research the effect of Renshen Pingfei prescription in the pulmonary fibrosis model induced by Silica in rat and discuss the possible mechanism. METHODS SD rats were anesthetized and injected with silica dust suspension into trachea to establish pulmonary fibrosis model，then randomly divided into model group， prednisone group， Renshen Pingfei prescription 3.0，6.0，12.0g/kg dose group， and establish normal group. Every day on time， the intragastric administration were proceeded for 48 days and lung tissue of rats were weighed to calculate pulmonary coefficient. Evaluating the inflammation and fibrosis of pulmonary alveoli through HE and Masson HE staining.The content of hydroxyproline（HYP） in lung tissue was detected by assay kit.The level of TGF-β1， NF-κB， PDGF， TNF-α and IFN-γ in alveolar lavage fluid were detected using ELISA-kit and the protein expression level of TGF-β1， Samd2/3 and ERK1/2 in lung were detected through immunohistochemical staining. RESULTS The kidney coefficient， the inflammation and fibrosis of pulmonary alveoli， the level of TGF-β1， NF-κB， PDGF， and TNF-α in alveolar lavage fluid the protein expression level of TGF-β1， Samd2/3 and ERK1/2 in lung were significantly decreased（P<0.05）in the pulmonary fibrosis model of rat after administration with Renshen Pingfei prescription， otherwise the level of IFN-γ in alveolar lavage fluid were significantly increased（P<0.05）. CONCLUSION Renshen Pingfei prescription has protective effect in pulmonary fibrosis and its mechanism may relate to TGF-β/Smad/ERK signal.