With the recent upsurge in obesity, the prevalence of nonalcoholic fatty liver disease (NAFLD) is growing globally. It is one of the most common causes of chronic liver diseases and abnormal liver function. The objective of this study was to investigate the influence of erythropoietin therapy on NAFLD and the role of transforming growth factor beta one (TGFβ1). NAFLD was induced in adult male albino Wistar rats by administration of methionine choline deficient (MCD) diet. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, bilirubin, body weight, liver weight and liver weight /body weight ratio were measured in different experimental groups to assess the liver affection. Liver samples were taken for measurement of malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor alpha (TNF-α) as well as histopathological detection of hepatic tissue injury and immuno-histochemical assessment of TGFβ1. NAFLD was found to produce a significant increase in serum level of AST, ALT, liver weight and liver weight /body weight ratio, accompanied with a significant increase in liver tissue (MDA and TNF-α) and TGF-β1 immuno-histochemical scoring, however, there was a significant decrease in hepatic GSH level. These results were supported by histopathological changes in hepatic tissues in the form of severe steatosis of hepatocytes and inflammatory cells infiltration. Meanwhile, these results were reversed by EPO treatment. EPO treatment showed a hepato-protective effects against the development of NAFLD with a significant preservation of liver functions and structure that can be explained by the anti-oxidant, anti-inflammatory and anti-fibrogenic effect of EPO treatment.