Increased level of inflammatory mediators plays a central role in the features of coronary artery diseases. As pentoxifylline could suppress the inflammatory process and has shown some promising beneficial effects in inflammatory diseases, we evaluated the effect of two months pentoxifylline administration in proteome of PBMCs of patients with coronary artery disease (CAD). A randomized placebo-controlled study was used. Fourteen CAD patients were randomized to 2 months of pentoxifyline treatment (1200 mg/day) (n=7) or placebo treatment (n=7). Blood samples were obtained before and after treatment. A comparative 2 dimensional gel electrophoresis was performed, and gels were silver-stained. Differentially expressed protein spots were detected and were identified by MALDI-TOF spectrometry. Six differentially expressed proteins were identified as HSP70, PPIA and α-Enolase, (all up-regulated) S100-A9, PIMT and β-5 tubulin (all down-regulated), most of which had previously been shown to play a potential role in the pathogenesis of atherosclerosis. As the blood mononuclear cell proteome responds to pentoxifylline with changes in a number of atherosclerosis-relevant proteins, it seems that pentoxifylline could be a good choice for future studies for prevention of cardiovascular events.