Abstract： Objective To evaluate the effect of erythropoietin (EPO) on cognitive function in rats with traumatic brain injury (TBI) and investigate its mechanisms. Methods Forty-eight SD rats were equally randomized into control, sham-operated, TBI and EPO+TBI groups. TBI models were established in the later 2 groups by operation and hydraulic shock. Sham-operated group received the operation only. The EPO+TBI group was injected with EPO immediately after the success of model making; the other groups were injected with saline at the same time. On the 30th d of injury, Morris water maze was employed to evaluate the cognitive function of the rats and the expression of brain-derived growth factor (BDNF) was detected by immunohistochemistry. Results In the navigation experiment, the latent period (the rats on founding the platform) in the control and sham-operated groups was significantly shorter than that in the other 2 groups (P<0.05); that in the TBI group was statistically longer than that in the EPO+TBI group (P<0.05). In the space searching experiment, the swimming times of the rats in each quadrant were significantly different (P<0.05): the control and sham-operated groups were the longest and the TBI group was the shortest of all the 4 groups. Immunohistochemistry showed that the expression of BDNF in the EPO+TBI group was significantly higher than that in the other 3 groups (P< 0.05). Conclusion TBI can damage cognitive function of the rats, while exogenous EPO may improve their memory abilities by up-regulating the expression of BDNF.