Objective: Carbon monoxide (CO) poisoning is one of the lethal intoxications all around the world. This poisoning obviously has mechanisms of toxicity beyond the formation of CO-Hb. The effects of CO are not restricted to the phase immediately after exposure. A delayed neurologic syndrome also has been reported. Soluble CO in the plasma causes a cascade of events which lead to lymphocytic immunologic response, microglia activity, and finally neurologic defects. Erythropoietin (EPO) has a critical role in the development and repair of the nervous system and also it exerts an incredible neuroprotection in cell culture and animal models. So we evaluate efficiency of erythropoietin as a treatment in carbon monoxide-poisoned rats. Materials and Methods: First the rats were exposed to 3000 PPM CO in air for 1 hour until they lost consciousness, and then different doses (625, 1250, 2500, 5000 and 10000u/kg) of EPO were administrated intraperitoneally (IP). After 24 hours, we determined S100β and GFAP (two astrocyte markers that release from the brain after injury) levels in the serum with commercial ELISA kits. About S100β we assessed the time algorithm of S100β raise after CO poisoning and after EPO administration. We also evaluated water content of brain as an indicator for edema. The effect of EPO on brain lipid peroxidation was determined by a colorimetric method too. Finally, we investigated if EPO could reduce the necrotic lesions in the brain after poisoning by pathological assessment. Results: EPO reduces the Malondialdehyde level in the brain tissue (as a marker of lipid peroxidation) and serum levels of GFAP and S100β, after CO poisoning. EPO clearly prevents the formation of necrotic lesions produced by poisoning but it can not reduce the water content of the edematous poisoned brain. Conclusion: Erythropoietin could be a new approach to Carbon Monoxide poisoning. More experiments in this regard are actively in progress.