1. Fibrin D-dimer is considered a consistent and independent marker of the risk of cardiovascular disease in population studies, as well as being related to atherosclerosis severity in patients. However, the role of fibrin D-dimer in macrophage-derived foam cell formation during atherogenesis remains unclear. 2. In the present study, using microarray techniques, we determined the effects of 100 ng/mL fibrin D-dimer fragments on macrophage cell function in atherosclerosis by investigating the expression levels of 128 genes related to the atherosclerotic pathophysiological processes. 3. The results showed that 27 genes were enhanced by D-dimer fragments to over twofold of control. These 27 genes belonged to six groups and included adhesion molecules, extracellular molecules, molecules related to lipid transport and metabolism, cell growth and proliferation molecules, transcription regulators and genes responsive to stress. We proceeded to determine the expression levels of five of these genes (intercellular adhesion molecule-1, matrix metalloproteinase-9, oxidized low-density lipoprotein receptor 1, vascular endothelial growth factor A and peroxisome proliferator-activated receptor alpha) using SYBR real-time polymerase chain reaction. The results confirmed gene upregulation, similar to the results obtained with the microarray, following treatment with D-dimer. 4. Therefore, the present study provides direct evidence regarding the pro-atherosclerotic role of D-dimer in macrophage function, which is mainly to enhance the inflammatory response during macrophage-derived foam cell formation.