Premature senescence of IMR-90 human diploid fibroblasts expressing telomerase (hTERT) establishes after exposure to an acute sublethal concentration of H 2 O 2 . We showed herein that p38 MAPK was phosphorylated after exposure of IMR-90 hTERT cells to H 2 O 2 . Selective inhibition of p38 MAPK activity attenuated the increase in the proportion of cells positive for senescence associated β-galactosidase activity. We generated a low density DNA array to study gene expression profiles of 240 senescence-related genes. Using this array, p38 MAPK inhibitor and p38 MAPK small interferent RNA, we identified several p38 MAPK -target genes differentially expressed in H 2 O 2 -stressed IMR-90 hTERT fibroblasts.