Background: To evaluate the time-dependent effects and pathophysiological mechanism of erythropoietin (Epo) on oxidative stress and liver injury resulting from obstructive jaundice in common bile duct-ligated rats. Methods: Wistar Albino rats were divided into 5 groups, each including 8 rats. The sham group underwent laparotomy only, while the Non-Epo-3 and Non-Epo-7 groups underwent common bile duct ligation and were sacrificed 3 and 7 days, respectively, after the operation. The Epo-3 and Epo-7 groups underwent common bile duct ligation and Epo treatment and were sacrificed 3 and 7 days, respectively, after the operation. Blood and tissue samples were collected from all groups for the determination of oxidative injury and hepatocellular damage. Serum total and direct bilirubin levels, alkaline phosphatase, reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA) and white blood cell counts were measured. Results: Significantly higher NO and MDA levels were found in Non-Epo groups than Epo groups. Significantly lower GSH levels were found in the Non-Epo-7 group than the Epo-7 and sham groups. Hepatocellular damage was also found to be reduced in Epo groups. Conclusions: In the present model, while common bile duct ligation increased oxidative injury and hepatocellular damage, treatment with Epo attenuated oxidative injury and hepatocellular damage by decreasing NO and increasing GSH.