In the present study, we investigated whether erythropoietin (Epo) has a protective effect against cytotoxicity induced by interferon-gamma (IFN-gamma ) and lipopolysaccharide (LPS) in primary rat oligodendrocyte cultures. The possible modulatory effect of erythropoietin on inducible nitric oxide synthase (iNOS) mRNA expression and nitrite production were also analyzed. Erythropoietin exerted a significant protective effect against IFN-gamma and LPS-induced oligodendrocyte injury as determined by lactate dehydrogenase assay. Treatment with erythropoietin inhibited the expression of iNOS mRNA and nitrite production resulting from proinflammatory stimulation by IFN-gamma and LPS. These results suggest that erythropoietin has protective effects against inflammatory oligodendrocyte injury in vitro and may play a protective role in neurological disorders characterized by oligodendrocyte death, such as multiple sclerosis.