Background: Acute kidney injury is of a high prevalence rate in acute myocardial infarction (AMI) patients. Erythropoietin (EPO) protects tissues from ischemia. Aim of the study: To investigate the possible cardiac and renal protective effects of EPO in a rat model of AMI and their mechanisms. Materials and Methods: 27 male adult albino rats were divided randomly and equally into 3 groups [control, myocardial infarction (MI) and MI pre-treated with EPO]. In control and MI groups, 2 ml saline were injected subcutaneously once every other day for 7 days. In MI pretreated with EPO group, rats were injected subcutaneously with 1000 IU/kg once every other day for 7 days. In the 6th and 7th days, rats in MI and MI pretreated with EPO groups were injected subcutaneously with isoproterenol (ISO) hydrochloride (150 mg/kg body weight /day), to induce MI. 1hr after the 2nd dose of ISO, ECG was recorded. Serum was separated from collected blood at the end of experiment for measurement of creatinine, TNF-α, MDA, LDH, IL-6, GSH and CK-MB. Cardiac and renal immunohistochemical study was done. Results: In MI group, increased cardiac and renal Bax immunostaining and increased serum level; of LDH, CK-MB, creatinine, IL-6, MDA and TNF-α were noticed, with a significant reduction in serum GSH in comparison with control group. In MI pretreated with EPO group, these changes were ameliorated. Conclusion: Erythropoietin has cardiac and renal protective effects in a rat model of AMI which is owed to its antioxidant, anti-inflammatory and antiapoptotic roles. Key words: Erythropoietin, Acute kidney injury, Myocardial infarction.