AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS) -induced pulmonary artery smooth muscle cell (PASMCs) injury and the role of heme oxygenase-1 (HO-1), and to explore the regulation mechanism of c-Jun N-terminal kinase (JNK) and activator protein-L (AP-1) signal transduction pathway in inducing HO-1 expression further.METHODS: Cultured PASMCs were randomly divided into 4 or 6 groups: normal culture group, LPS (10 mg/L), CCK-8(10-6 mol/L) plus LPS (10 mg/L) group, CCK-8 (10-6 mol/L)group, zinc protoporphyrin 9 (ZnPPIX) (10-6 mol/L) plus LPS (10 mg/L) group, CCK-8 (10-6 mol/L) plus ZnPPIX and LPS (10 mg/L) group. Seven hours after LPS administration,ulterstructrual changes and content of malondialdehyde (MDA) of PASMCs in each group were investigated by electron microscopy and biochemical assay respectively.HO-1 mRNA and protein of PASMCs in the former4 groups were examined by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry staining.Changes of c-fos expression and activation of JNK of PASMCs in the former 4 groups were detected with immunocytochemistry staining and West blot 30 min after LPS administration.RESULTS: The injuries of PASMCs and the increases of MDA content induced by LPS were alleviated and significantly reduced by CCK-8 (P＜0.05). The specific HO-1 inhibitorZnPPIX could worsen LPS-induced injuries and weaken the protective effect of CCK-8. The expressions of c-fos,p-JNK protein and HO-1 mRNA and protein were all slightly increased in LPS group, and significantly enhanced by CCK-8 further (P＜0.05).CONCLUSION: HO-1 may be a key factor in CCK-8attenuated injuries of PASMCs induced by LPS, and HO-1expression may be related to the activation of JNK and activator protein (AP-1).