Objective: To study the effect of chronic hypoxia on pulmonary arterial remodeling and Krüppel-like zinc-finger transcription factor 5 (KLF5) protein expression in pulmonary artery smooth muscles in a hypoxia-induced pulmonary hypertension model. Methods: Totally 20 adult SD rats (200-250 g) were divided into a normoxia group and a chronic hypoxia group by the random number table. Rats in the chronic hypoxia group were put in an automatic hypoxia box for 21 days. After that, right ventricular systolic pressure (RVSP), mean right ventricular pressure (mRVP) and RV/(LV+ S) were measured. Lung tissue sections were made. The lumen area, ratio of wall thickness to radius of pulmonary artery were gauged by using the Image Pro Plus software. Primary PASMCs were cultured in oxygen-deficient environment (4% O2)or normal oxygen environment (21% O2)for 60 hours respectively, and then total protein or RNA were extracted for Western blotting and Q-PCR analysis.KLF5 protein expression in rat pulmonary arterial smooth muscle and pulmonary arterial smooth muscle cells was detected by Western blot. Results: Compared with the normoxia group(28.3±0.4), (11.3±1.0)mmHg (1 mmHg=0.133 kPa), the RVSP and mRVP in the chronic hypoxia group [(43.9±1.3), (26.5±2.3)mmHg] were significantly increased(P<0.05). The Rv/(LV+ S)of the chronic hypoxia group was(0.48±0.03), markedly higher than that of the normoxia group(0.27±0.01, P<0.05). The luminal area/total area of artery in the chronic hypoxia group decreased to (46.1±6.6)% compared with that in the normoxia group [(68.73±3.06)%, P<0.05]. The wall thickness/arterial radius(WT%)of the chronic hypoxia group increased up to (5.64±0.32)% as compared with (3.7±0.4)% of the normoxia group (P<0.05). The level of KLF5 protein in pulmonary arterial smooth muscles of the chronic hypoxia group was (21.6±7.2) times that of the normoxia group (P<0.05). Conclusion: Hypoxia induced the increase of RVSP, mRVP, RV/(LV+ S), accompanied with pulmonary arterial remodeling. The underlying mechanism of the artery change may be related to up-regulated expression of KLF5.