During last years, the number of patients who have been continuously treated by peritoneal dialysis (PD) for over 5 or 10 years has markedly increased. Sclerosing syndromes and membrane failure are the most common complications that are now currently observed in long-term PD patients. Exposure to conventional PD fluids (PDFs) with poor biocompatibility induces a kind of «chemical peritonitis» in response of bad «biotolerance». The peritoneal fibroblasts, mesothelial cells and especially endothelial cells function as a filtration barrier, but also control intraperitoneal inflammation as well as leukocytes and macrophages. Peritoneal exposure to conventional poorly biocompatible PDFs which combine non-physiological pH, high glucose concentrations, and high levels of glucose degradation products (GDPs), is associated with an accelerated peritoneal aging. Heat sterilization of PDFs induces the formation of GDPs which are involved in the formation of advanced glycation end-products (AGEs). Glucose, GDPs and AGEs participate to the peritoneal membrane failure and aging. AGEs via RAGE (receptor for AGEs) are involved in human peritoneal mesothelial cell (HPMC) activation. In the present work, we summarize our previous in vitro works regarding mesothelial RAGE implication in the peritoneal membrane aging. Two periods of aging are distinguished: i) early peritoneal changes related to mesothelial cell activation and loss, ii) late membrane alteration correlated to submesothelial fibrosis and neovascularization.