Objective:To investigate the effects of early use of recombinant human tumor necrosis factor receptor-Fc fusion protein(rhTNFR-Fc) on pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats,and to explore its mechanism. Methods:Total 24 adult male rats were randomly divided into control group (C group),rhTNFR-Fc group (R group),MCT group(M group) and rhTNFR-Fc combined monocrotaline group(M+R group). PH was induced by intraperitoneal administration of MCT at a concentration of 60 mg/kg for the rats of M group and M+R group on day 1. rhTNFR-Fc(0.4 mg/kg) or saline(1 ml) was injected subcutaneously every other day for day 2 to day 21. After 3 weeks,the mean pulmonary arterial pressure(mPAP),tha ratio of right ventricle to left ventricle and septum[RV/(LV+S)] were measured,microscope was used to detect the morphologic changes of small pulmonary arteries as calculating the percentage of vascular wall thickness to vascular external diameter(WT%). The expression of Tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in lung homogenates were measured by ELISA method,and the protein level of NF-κB in lung tissue was measured by Western blot. Results:① The levels of mPAP, RV/(LV+S) and WT% were higher in M group than those in C group,and early-use of rhTNFR-Fc can inhibit the increase of mPAP and the rise of WT% in MCT-induced rats(P < 0.05). ② rhTNFR-Fc can inhibit the increase of IL-6 and TNF-α in lung of the rats induced by MCT(P < 0.05). ③ rhTNFR-Fc can inhibit the increased expression of NF-κB in pulmonary tissue of MCT-induced rats(P < 0.05). Conclusion: These results suggest that rhTNFR-Fc can ameliorate the progression of PAH induced by MCT in rats,which was probably through inhibiting NF-κB signal pathway and decreasing inflammatory cytokines expression of IL-6 and TNF-α.