Aspirin and other non-steroidal anti-inflammatory drugs show efficacy in the prevention of colon cancer. The mechanism by which they do this is unclear. We used a commercially available DNA microarray to study changes in gene expression in 1176 cancer related genes in the HT29 colon cancer cell line induced by aspirin. Overall we find more genes that are significantly induced than are repressed. The pattern of gene expression changes is different at high concentrations of aspirin (5 mM) than at lower levels (500 and 50 microM). Genes involved in DNA damage signaling, nucleotide metabolism and the stress response are induced, and cell cycle related genes repressed. The small GTPase Rac1 is highly induced and this was confirmed by immunoblotting. We show using immunohistochemistry that Rac1 is expressed in mature colonocytes at the intercrypt table in human and mouse colon tissue. These results support the previous findings that aspirin has different actions at high concentrations than at low concentrations and further show the use of DNA array technology in the investigation of drug mechanisms of action. Furthermore, they point towards a role for Rac1 in the action of aspirin in colon cancer.