Objective To investigate the effect of Ras on the gene expression during proliferation of human femoral artery smooth muscle cells. Methods Human femoral artery smooth muscle cells were transfected with recombinant adenovirus-mediated active and negative mutants of Ras gene (AdRasV12 and AdRasN17 respectively), and the gene expression profile was determined by Affymetrix GeneChip. Results After transfection with AdRasN17, 120 genes were identified with significantly altered expression, among which 43 genes were up-regulated and 77 genes were down-regulated. While in counterparts of AdRasV12, 231 genes were identified as differentially expressed, among which 127 genes were up-regulated and 104 were down-regulated. These genes were functionally categorized as cell cycle and apoptosis categories, signal transduction, metabolism and response to stimulus. Conclusion The active and negative mutants of Ras may alter the gene expression of human femoral artery smooth muscle cells, and these gene targets may be involved in abnormal arterial smooth muscle cell proliferation in cardiovascular diseases such as atherosclerosis and restenosis.