Abstract: Objective To study the effect of endothelin receptor antagonist（ETP-508） on substance P（SP） and matrixmetallop roteinase-2（MMP-2） in lung fibrosis tissue of experimental rats. Methods Rats were divided into bleomycin（BLM） group, ETP-508 group and control group. A lung fibrosis model was induced by endotracheal injection of BLM（5mg/kg） for BLM and ETP-508 groups. Rats in control group received an equivalent endotracheal injection of 0.9% sodium chloride. On the next day, rats in ETP-508 group were treated with intraperitoneal injection of ETP-508（100μg/kg, every other day） while those in control and BLM groups received an equivalent endotracheal injection of 0.9% sodium chloride. Rats were killed on day 7 and 28, respectively. SP, MMP-2 and hydroxyproline（HYP） levels in their lung tissue were measured and histopathological change was observed. Results The HYP level was significantly higher in lung tissue of BLM group than in that of control group（P＜0.01）. Lung fibrosis occurred in BLM group. The mean SP level was higher in lung tissue of BLM group than in that of control and ETP-508 groups on day 7 and 28（P＜0.01）. The MMP-2 level was lower in BLM group on day 28 than on day 7 and than in control and ETP-508 groups（P＜0.01）. No significant difference was found in SP and MMP-2 levels between control and ETP-508 groups on day 7 and 28（P＞0.05）. Conclusion ETP-508 can inhibit the formation of lung fibrosis by reducing the level of SP and suppressing the degradation of MMP-2.