Erythropoietin treatment decreases portal hypertension and splanchnic hypermetabolism in a rat model of portal hypertension. In patients with liver cirrhosis and portal hypertension, erythropoietin (Epo) treatment has been shown to have different therapeutic effects according to the severity of the disease. In the present study, the effects of Epo administration in a rat model of portal hypertension (BDL model) were evaluated by measuring portal pressures and the metabolic alterations of the hepatic parenchyma. Portal hypertension was induced by partial ligation of the common bile duct (BDL), and chronic Epo treatment was started after 10 days. Epo was administered intravenously, via osmotic pumps, for one month, during which time a significant decrease in portal pressure, decrease in portal perfusion, and reduction of splanchnic hypermetabolism were observed. Chronic Epo treatment significantly decreased plasma glucose and insulin levels and insulin resistance. In addition, lipid metabolism and liver steatosis were significantly improved. Treatment with Epo improved the liver cirrhosis induced by BDL, showing significant effects on the maintenance of normal portal pressure and the improvement of hepatocellular dysfunction and liver injury. The present study shows that Epo treatment improves the biochemical alterations induced by BDL, including hepatomegaly, metabolic disorders and abnormal biochemical profile, and it also provides beneficial effects in the cardiovascular repercussion of the liver disease. The Epo treatment was capable of correcting the metabolic disorders in an experimental model of liver cirrhosis, contributing to a better understanding of the effects of Epo on the liver and the pathophysiology of chronic liver diseases.