Aim To study the effect of serum interleukin-18 （IL-18） in human acute myocardial infarction and its possible mechanism in the process of plaque rupture. Methods Serum levels of IL-18 and MMP-9 proteins were determined using commercially available enzyme-linked immunoassays in each group: acute myocardial infarction （AMI） group, stable angina pectoris （SAP） group and heathy control group （n＝20, respectively）. Flow cytometry was applied to assess extracellular matrix metalloproteinase inducer （EMMPRIN） expression on the surface of monocytes of each group. In vitro experiment, quantitative real-time polymerase chain reaction （QRT-PCR） and Western blot were performed to compare EMMPRIN expression of monocytes cultured in presence and absence of IL-18. Results In patients with AMI, serum level of IL-18 and MMP-9 and expression of EMMPRIN on monocytes markedly increased compared with patiens with SAP and heathy control group. Furthermore, increased level of IL-18 was positively associated with elevated expression of EMMPRIN on monocytes in AMI group （r²＝0.57, P<0.001）. The data proved that expression of EMMPRIN was enhanced in monocytes cultured in presence of IL-18 （P<0.05）. Conclusion IL-18 stimulates monocytes to express EMMPRIN, which may induce secretion of MMP-9, contributing to atherosclerotic plaque instability and rupture.