Erythropoietin (EPO), a glycoprotein, plays an important role in erythropoiesis and neuroprotection. EPO therapies for anemia or neurodegenerative diseases require frequent injections or high-dose systemic administration which may cause unwanted side effects. Various strategies for EPO delivery have been investigated for increasing EPO bioavailability and decreasing side effects, including nano/micro particles, PEGylation of EPO and transport-mediated delivery systems. Nano/micro particles provide EPO with long-term effect and protect EPO against proteolytic cleavage. PEGylated EPO prolong circulating time and reduce injection frequency of anemia treatment. A transport-mediated delivery system enables protein to cross biological barriers. Presently, there is no report about an effective delivery system of EPO for neuroprotection. This review focuses on EPO delivery systems for erythropoiesis or neuroprotection with prolonged duration and enhanced bioavailability.