Abstract： Objective To investigate the effect of down-regulating epidermal growth factor receptor (EGFR) expression on Bleomycin induced pulmonary fibrosis in mice.Methods Forty 4 ～6 week aged C57BL/c male mice were randomly divided into control,bleomycin,bleomycin plus EGFR RNAi groups and RNAi negative control group.Bleomycin group were treated with bleomycin (3 mg/kg) by endotracheal injection on day 0,control group were treated with PBS.And bleomycin plus EGFR RNAi group were received EGRF siRNA plus bleomycin intratracheal administration.RNAi negative control group received negative EGRF siRNA plus bleomycin intratracheal administration.Mice were sacrificed 10 days after the treatments.Hydroxyproline (HYP) assay was performed in the lung tissue.The lung tissue slides were examined pathologically with H.E.staining,and EGFR mRNA expression was detected by reverse transcriptasepolymerase chain reaction (RT-PCR) technique.Western blot were performed to identify the protein level.of total EGFR and phosphorylated EGFR.Results Histological examination of lung specimens demonstrated that EGFR siRNA administration lessened lung fibrosis induced by bleomycin and significantly reduced HYP content (543.00±25.89 vs 900.73±31.77,P＜0.01).EGFR mRNA (0.31±0.05 vs 0.75±0.08,P ＜0.01) and protein expression(1.53±0.47 vs 2.56±0.37,P ＜0.01) in EGFR siRNA-treated mice was significantly decreased.The expression of phosphorylation of EGFR protein (1.78±0.35 vs 2.84±0.51,P ＜0.01) and EGFR protein in RNAi group was less than in bleomycin group.Conclusions EGFR RNAi reduced the BLM-induced lung fibrosis by inhabiting EGFR activation.