In this study, the effect of dexamethasone, a synthetic glucocorticoid, on H(2)O(2) stimulated murine RAW264.7 macrophages was investigated. It was found that dexamethasone protected the cells from apoptosis induced by H(2)O(2). A cDNA microarray, which consists of 1000 genes selected from a mouse clone set provided from NIA, was used to study the gene expression profiles involved in the protective effect. Our data show that dexamethasone exerts the anti-apoptosis function by changing the expression patterns of many genes involved inhibiting the up-regulation of apoptosis promoting genes and the down-regulation of cell cycle stimulating genes as well as keeping the up-regulation of cell survival related genes. Our study also revealed that dexamethasone protects RAW264.7 macrophages from H(2)O(2) induced apoptosis through blocking nuclear factor-kappa B (NF-kappaB) activity.