Erythropoietin (EPO), a haematopoietic growth factor has been reported to display neuroprotective properties in different animal models. In the present study, we investigated the neuroprotective effects of EPO on Aβ 25–35 -induced neuronal toxicity and its potential mechanisms in PC12 cells. Aβ 25–35 significantly reduced cell viability and increased the number of apoptotic-like cells. In addition, increased ROS production and decreased mitochondrial membrane potential were also found after Aβ 25–35 exposure. All of these phenotypes induced by Aβ 25–35 were markedly reversed by EPO. Pretreatment with EPO prior to Aβ 25–35 exposure significantly elevated cell viability, reduced Aβ 25–35 -induced apoptosis, decreased ROS production, and stabilized mitochondrial membrane potential. Furthermore, EPO also attenuated the downstream cascade following ROS, including Bcl-2/Bax, and caspase-3 activation. Our results suggest that EPO holds potential for neuroprotection and therefore, may be promising for the treatment of Alzheimer's disease.