To determine the chronic effects of heavy ion irradiation, an antibody based proteomic microarray technology was applied to monitor alterations in the serum proteome, six months after whole body irradiation of adult male C57Bl/6 mice with 0.5 Gray of (56)Fe. Out of 507 proteins, irradiation reduced expression of 25 proteins and enhanced expression of 12 proteins in serum (> 5% change relative to sham-irradiated controls). Of the 25 proteins found to be down-regulated, Poly ADP Ribose Polymerase (PARP) was 13% lower in the 0.5Gy mice and among the up-regulated proteins, beta-Tubulin was found to be 10% higher in the 0.5Gy group compared to the sham-irradiated 0Gy controls. Thus, irradiation with a relatively low dose of heavy ions caused persistent and selective changes in serum levels of proteins that are typically intracellular, suggesting chronic genotoxic damage.