There is accumulating evidence that supports a role of infection in atherosclerosis, with possible mechanism by injuring to the endothelium and inducing an autoimmune response to heat shock proteins (HSPs). In this study, a cDNA array, containing 588 human cardiovascular genes, was utilized to analyze the gene expression profile of Chlamydia pneumoniae (C. pneumoniae) infected human umbilical vein endothelial cells (HUVECs). After 48h of C. pneumoniae infection, the HUVECs were harvested and subjected to immunofluorescent staining, electron microscopy, cDNA array hybridization, RT-PCR, and immunoblotting. This study found a panel of human host genes that were upregulated by C. pneumoniae. The majority of these genes were related to complex lipid metabolism, adhesion receptors, hormones, hormone receptors, and a metalloproteinase that may contribute to atherosclerosis in vivo. Representatives of upregulated gene products, i.e., heat shock protein 60 (HSP60), macrophage scavenger receptor, cytochrome P450, and VEGF165R were immunofluorescently detected in HUVECs, with their greater expression induced by C. pneumoniae infection. These findings supported the opinion that C. pneumoniae might contribute to atherosclerotic development in vivo.