Abstract: Objective To investigate the effect of calpain-2 and caspase-3 on pulmonary fibrosis and the protective effect of Danshaohuaxian(DSHX) capsule on pulmonary fibrosis in rats.Methods Thirty SD rats were randomly divided into control group,pulmonary fibrosis model group,and DSHX capsule treatment group.Pulmonary fibrosis model was induced by intratracheal instillation of single dose bleomycin(5 mg/kg).DSHX capsule of 0.8 g/kg was administered daily by oral to the treatment group at the second day after bleomycin exposure.All rats were killed on the 28th day.Immunohistochemistry was used to detect the expression of calpain-2 and caspase-3 protein.The expression of calpain-2 and caspase-3 mRNA were detected by real-time PCR.Results The expression of calpain-2 protein (0.35±0.06),calpain-2 mRNA (210±86),caspase-3 protein(0.41±0.12),and caspase-3 mRNA(614±106) in the rats of molel group were higher than those in the control group (P< 0.01).After the treatment of DSHX capsule,the expression of calpain-2 protein (0.18±0.03),calpain-2 mRNA(97±71),caspase-3 protein(0.22±0.04),and caspase-3 mRNA(315±92) were lower than those in the model group(P< 0.05,P< 0.01).Conclusion Calpain-2 and caspase-3 play an important role in the process of pulmonary fibrosis.DSHX capsule could reduce pulmonary fibrosis induced by bleomycin,and its mechanisms may include the expression of calpain-2 and caspase-3.