Background: Erythropoietin (EPO) is a glycoprotein hormone member of the type 1 cytokine super family that is produced by renal cortical and outer medullary type 1 fibroblasts in response to tissue hypoxia. It has a hematopoietic function, but recent studies have shown that EPO has several non hematopoietic functions. EPO limits the destructive potential of tumor necrosis factor α and other proinflammatory cytokines in different tissues. Objective: Studying the possible protective and curative effects of EPO on diabetes in alloxan-induced diabetic rats. Material and methods: Fifty adult male albino rats of local strain between 7-8 weeks old and weighing 140-160 g were used. The rats were divided into 5 equal groups. Group I (control group), Group II (erythropoietin- treated group), Group III (diabetic group), Group IV (EPO- pretreated diabetic group), and group V (EPO-treated diabetic group). The body weight, food consumption, blood glucose level, serum tumor necrosis factor α (TNF-α) and serum interleukin 6 (IL-6) were determined for all groups. Results: Blood glucose level, serum tumor necrosis factor α (TNF-α) and serum interleukin 6 (IL-6) decreased in EPO-pretreated and treated diabetic groups when compared to the diabetic rats. These results were confirmed by the histopathological study which showed marked improvement of the destructive effect on pancreatic islet cells induced by alloxan especially when EPO treatment was given after two weeks of alloxan injection. Conclusion: EPO is a general tissue protective cytokine. It acts on glucose metabolism and increasing β cell mass. Thus, promotion of EPO signaling in β cells may be a novel therapeutic strategy for diabetes prevention and treatment.