〔Abstract〕 Objective To investigate the expression of leptin on hypoxia-inducing factor-1α (HIF-1α)/nuclear factor-kappa B (NF-κB) in rat airway smooth muscle cells (ASMCs) under hypoxia condition and its effect on cell proliferation. Methods Rat ASMLs were cultured in vitro, the cells were divided into hypoxia group, leptin + hypoxia group (L200 group), leptin + hypoxia + HIF-1α inhibitor group (2ME2 group), leptin + hypoxia + NF-κB inhibitor group (PDTC group) Leptin + hypoxia + HIF-1α inhibitor + NF-κB inhibitor group (2ME2 + PDTC group) according to random number table method. After incubation for 24 h, the cell proliferation rate was detected by CCK-8 method, and the expressions of HIF-1α and NF-κB protein and mRNA were detected by Western blot and real-time polymerase chain reaction (PCR). Results The protein and mRNA expressions of HIF-1α and NF-κB in L200 group were increased compared with that in hypoxia group. Compared with L200, the protein and mRNA expressions of HIF-1α and NF-κB in 2ME2, PDTC and 2ME2 + PDTC groups were decreased, and the decreases were most significant in 2ME2 + PDTC group, the differences were statistiacally signficiant (P < 0.01). Cell proliferation in L200 group was significantly higher than that in hypoxia group. Compared with L200, cell proliferation in 2ME2, PDTC and 2ME2 + PDTC groups was decreased, and the decrease was more significant in 2ME2 + PDTC group. The cell proliferation of 2ME2 + PDTC group was decreased compared with hypoxia group, and the differences were statistically significant (P < 0.01). Conclusion Leptin can promote the proliferation of airway smooth muscle cells by partially activating the expression of HIF-1α/NF-κB, thus playing a certain role in the formation of airway remodeling.