This study investigated the frequency of apoptosis in rat pulmonary epithelial cells after intraperitoneal endotoxin (LPS) injection, the effects of LPS on inflammatory markers [myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha), and vascular endothelial growth factor (VEGF)l in lung damage and the protective effects of two known antioxidant agents, erdosteine and N-acetylcysteine (NAC). Mate Wistar rats were divided into six groups, each composed of nine rats: two control groups, two LPS-treated groups, one erdosteine-treated group (150 mg/kg), and one NAC-treated group. LPS was intraperitoneally injected at a dosage of 20 mg/kg. Following LPS injection, the antioxidants were administered orally. The rats were killed 24 h after LPS administration. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. Apoptosis level in epithelial cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-a in epithelial cells and VEGF in endothelial cells, and epithelia] MPO activity were evaluated by immunohistochemistry. Posttreatment with erdosteine and NAC significantly reduced the rate of LPS-induced epithelial cell apoptosis. Posttreatment with erdosteine and NAC significantly reduced the increases in the local production of TNF-alpha and VEGF, and epithelial MPO activity. The effects of NAC on apoptosis, the increases in the local production of TNF-a and VEGF, were weaker than the effects of erdosteine. This finding suggests that the effects of erdosteine at the administered dose on apoptosis regulation are stronger than that of NAC. (c) 2006 Elsevier Ireland Ltd. All rights reserved.