Human cytomegalovirus (HCMV) infection may be involved in the pathogenesis of atherosclerosis by modulating functions of smooth muscle cells (SMC). In this study, we performed an oligonucleotide microarray screening of 780 inflammation-associated genes in HCMV-infected aortic SMC (AoSMC). The expression of 31 genes was stimulated and 24 genes were down-regulated following infection with HCMV strain DC-134. Following infection with HCMV strain AD-169 infection, we found 24 genes to be stimulated and 32 genes to be down-regulated. Among these were primarily genes encoding for CC and CXC chemokines, adhesion molecules, and tumor necrosis factor (TNF) receptor superfamily members, apoptosis-related factors, signal transduction molecules and transcription regulators. The up-regulated genes included matrix metalloproteinase (MMP)-1 and MMP-3 in HCMV infected cells. Using RT-PCR and enzyme immunoassay we found stimulated expression of MMP-1 (3.2-fold expression) and MMP-3 (334-fold expression) in HCMV strain DC-134-infected AoSMC at 72 h following infection.The findings of our study suggest that HCMV infection of AoSMC cause an activation of atherosclerosis-relevant factors in SMC. The increased expression of MMPs which have been shown to be involved in atherosclerotic plaque rupture and myocardial infarction is in agreement with the hypothesis that this pathogen might contribute to plaque inflammation in atherosclerotic disease.