Objective(s) Erythropoietin has been shown to exert neuroprotective effects in a variety of CNS injury models. Elevation of serum S100 beta, as a glial damage marker and myelin basic protein (MBP) has been reported to occur in acute carbon monoxide (CO) poisoning. The aim of this study was to evaluate the effect of erythropoietin (EPO) on serum S100 beta and MBP levels after CO poisoning in rats. Materials and Methods Rats were poisoned with a mixture of 3000 PPM CO in air for 65 min. After exposure, half of the rats received 5000 u/kg EPO and the rest received normal saline. At 3, 6, 12, 24, 48, 72, 144, and 336 hr after exposure samples were taken. Additionally, EPO was administered at three lower doses (625, 1250 and 2500 u/kg). The serum s 1 cop and MBP levels were measured using immunoenzymatic colorimetric assay. Hemoglobin level was alsomeasured. Results Serum S100 beta levels in CO poisoned rats were significantly higher compared to the control group [6 hr (P< 0.01), 12 hr (P< 0. 001), 24 hr (P< 0.001), 48 hr (P< 0.008) and 72 hr (P< 0.008)]. EPO administration could significantly prevent serum S100 beta elevations after 12 hr (P< 0.008) and 24 hr (P< 0.008) of CO poisoning. Serum MBP levels in CO poisoned rats were not significantly increased in comparison with the control group (P> 0.05). EPO significantly increased the hemoglobin levels. Conclusion EPO could partially prevent neuronal damage. More studies are required to elucidate other aspects of these effects.