Aim In order to find out the mechanism that macrophage colony-stimulating factor protects monocytes/macrophages from oxidative injury. Methods We used macrophage colong-stimulating factor(MCSF)-riched L929 cell conditioned medium (L929-CM) to investigate the effect of MCSF on glutathione peroxidase (GPx) gene expression in RAW264.7 cells applying enzyme activity determination and reverse transcription polymerase chain reaction (RT-PCR) technique. Results It showed that MCSF could improve selenium-dependent glutathione peroxidase (SeGPx) and non-selenium-dependent glutathione peroxidase (non-SeGPx) activity in RAW264.7 cells. MCSF could also increase plasma glutathione peroxidase (PLGPx) mRNA expression in the cells. However, there was no induction of phosphalipid hydroperoxide glutathione peroxidase (PHGPx) expression by MCSF. Conclusion MCSF might protect monocytes / macrophages from oxidative injury through improving antioxidant enzymes activities and gene expression.