AIM: To observe the role of c-fos in the protection by cholecystokinin-octapeptide (CCK-8) against pulmonary artery smooth muscle cell (PASMC) injury induced by lipopolysaccharide (LPS). METHODS: The ultrastructure of PASMC was observed under transmission electron microscope (TEM). MDA content,LDH release and the rate of trypan blue in PASMC were measured,and immunocytochemistry technique was adopted to observe the c-fos protein expression. RESULTS: The TEM results showed significant PASMC structural injury in LPS group and alleviated structural changes in LPS+CCK-8 group. CCK-8 reduced the increase in the rate of trypan blue uptake,MDA content and LDH release in PASMC induced by LPS. LPS lightly increased c-fos protein expression,which was enhanced by CCK-8. CONCLUSION: CCK-8 attenuated the injury of PASMC induced by LPS,which may be concerned with the increase in c-fos protein expression.