Peritoneal dialysis (PD) is an alternative treatment of patients with end-stage renal disease. Unfortunately, long term peritoneal dialysis causes injury of the peritoneum associated with ultra filtration failure. Erythropoietin (EPO) is a potent stimulator of elytroid progenitor cells and its expression is enhanced by hypoxia. The aim of the present study was to evaluate the effect of EPO on the development of experimental peritoneal fibrosis induced by chlorhexidine gluconate (CG). A peritoneal fibrosis model was established using rats treated intraperitoneally with injection of CG. EPO was administered at the dose of 5000 U/kg i.p. three time per week for three weeks. When compared to CG-treated rats, EPO (5000 U/kg i.p. three time per week for three weeks) treated rats subjected to GC-induced peritoneal fibrosis experienced a significantly lower rate in the extent and severity of the histological signs of peritoneal injury. EPO also caused a substantial reduction of (i) the rise in myeloperoxidase activity (mucosa), (ii) the expression in the tissue of TNF-alpha, TGFbeta and VEGF (iii) the increase in staining (immunohistochemistry) for nitrotyrosine and for PAR, as well as (iv) the NF-kappaB activation caused by CG in the peritoneum. Thus, EPO treatment reduces the degree of peritoneal fibrosis caused by CG. We propose that this evidence may help to clarify the potential therapeutic actions of EPO in patients with peritoneal fibrosis.