Abstract： Objective To study the mechanisms of pulmonary hypertension caused by smoke exposure in researching the effect of smoke exposure on the expressional levels of hypoxia inducible factor1α (HIF-1α) and nuclear factor-κB (NF-κB) p65 in rats lungs.Methods 32 male Wistar rats were divided randomly into control group,smoke exposure 4,8,12 weeks group.The rat models of all groups were established by smoke exposue.The mean pulmonary arterial pressure (mPAP) was measured by rightheat catheterization.,and right ventricle hypertrophy index (RVHI) was measured. The relative expression of HIF-1α mRNA was detect by fluorescence quantitative PCR and HIF-1α,NF-κB p65 protein in rat lungs were detected by immunohistochemistry in all rats of four groups.Results ① The mPAP of rats of smoke exposure 8 and 12 weeks groups were significantly higher than those of the control group ( P ＜0.05),and the right ventricular hypertrophy was found after 8 weeks of smoke exposure,the RVHI in smoke exposure 12 weeks group was significantly higher than those others ( P ＜0.05).②The relative expression of HIF-1α mRNA of rats in smoke exposure 8 and 12 weeks groups were significantly higher than those of smoke exposure 4 weeks and the control group (all P ＜0.05).③ The expression of HIF-1αprotein in the pulmonary vascellum smooth muscle and NF-κB p65 protein were significantly higher than those of the control group (all P ＜0.05).④ The expressions of HIF-1α protein were positively correlated with mPAP,RVHI,the relative expression of HIF-1α mRNA and NF-κBp65 protein.Conclusions Smoke exposure increase the expession level of HIF-1α and the NF-κB,HIF-1α has an important play on pathogenesis of pulmonary hypertension caused by smoke exposure.