Hypoxic-ischemic brain damage (HIBD) occurs due to intrauterine hypoxia ischemia influencing the energy supply for fetal brain cells, which affects the metabolism of the brain to make the brain suffer a severe damage. Erythropoietin (EPO), which regulates hemacytopoiesis, is a kind of cytokine. EPO is sensitive to hypoxia ischemia. In this study, we aimed to investigate the effect of EPO on the expression of Fas/FasL in brain tissues of neonatal rats with HIBD. Neonatal rats were assigned randomly to sham, HIBD, and EPO groups. Five time points for observation were 6, 12, 24, 48, and 72 h after the HIBD rat model had been established, respectively. In the HIBD group, Fas/FasL expression began to rise at 6 h, reached the peak at 12-24 h, and dropped from 24 h. In the EPO group, the expression of Fas/FasL was lower than those in HIBD group at 12, 24, and 48 h (P<0.05). Our findings suggest that EPO may reduce cell apoptosis after hypoxic-ischemic damage through reduction of the expression of Fas and FasL, and that optimal therapeutic time window is 6-24 h after HIBD.