Premature senescence of IMR-90 human diploid fibroblasts expressing telomerase (hTERT) establishes after exposure to an acute sublethal concentration of H2O2. We showed herein that p38MAPK was phosphorylated after exposure of IMR-90 hTERT cells to H2O2. Selective inhibition of p38MAPK 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, p38MAPK inhibitor and p38MAPK small interferent RNA, we identified several p38MAPK-target genes differentially expressed in H2O2-stressed IMR-90 hTERT fibroblasts. © 2006 Federation of European Biochemical Societies.