Abstract: Objective?To study the profile of IGF2R expression and histone modifications in replicative cell senescence. Methods?The changes of biological characteristics of young human pulmonary fibroblast (HPF) cells 〔at population doubling level (PDL) 23〕 and aging HPF cells (at PDL50) were observed and real-time quantitative PCR was utilized to investigate human IGF2R gene expressions profile during the process of cellular aging (at different PDL). Then chromatinimmunoprecipitation-real time quantitative PCR (CHIP-QPCR) methods were conducted to analyze histone modifications of the regions around the transcriptional start site of IGF2R (H3-Ac, H3K9-tri-Me, H3K9-Ac and H3K4-tri-Me). Results?In contrast to young cells, the aging cells were bigger and less proliferative, their cell cycles arrest, and aging specific β-galactosidase staining was positive. IGF2R gene expression was in positive correlation with PDL. H3-Ac, H3K9-Ac and H3K4-tri-Me were dominant in the upstream region (-0.6 kb) to the downstream region (+1.2 kb) of transcriptional start site (TSS). While in the downstream of TSS from +1.6 kb to +4.0 kb, H3K9-Ac was declined and H3K9-tri-Me was elevated in turn, but H3K4-tri-Me still prevailed in these areas. Conclusion?IGF2R is related to cell replicative senescence and its gene expression is regulated by histone modification of H3. Therefore, epigenetics may play a role in cell senescence.