Abstract： Objective To investigate the effects of carbamylated erythropoietin (C-EPO) on brain edema in traumatic brain injury (TBI) rats coupled with seawater drowning(SWD).Methods Totally,108 male SD rats were randomly divided into the sham group(n =30),the TBI + SWD group (n =36)and the C-EPO treatment group (n =36).The TBI + SWD rat model was established by using Marmarou brain trauma method (450 g × 1.5 m),coupled with the pumping of artifical seawater into trachea at a rate of 3ml/kg.Following building of the composite model,50 μg/kg of C-EPO or an identical volume of normal saline were injected into the abdomen every 24 hours.Samples of brain tissue were collected at 6,24,72 and 168 hours after surgery.Neurologic impairment and recovery of the rats were evaluated by MNSS.At the same time,pathological changes in the injured brain tissue,water content in the brain tissue,permeability of blood brain barrier (BBB) and the expression of AQP4 were either closely observed or detected.Results Seventy-two hours after surgery,HE staining indicated that brain edema could clearly be observed in the TBI + SWD group,and brain edema in the C-EPO treatment group was obviously less severe,as compared with the TBI + SWD group.As compared with the TBI + SWD group,MNSS scores of the C-EPO treatment group at hours 24,48,72 and 168 all decreased (P ＜ 0.05).Furthermore,brain water content at hours 24,48,72 and 168 after surgery in the C-EPO group all significantly decreased,and EB content at hours 6 and 72 after surgery in the C-EPO group also significantly decreased,as compared with those of the TBI + SWD group(P ＜ 0.05).Besides,the expression levels of AQP4 at hours 6,24,72 and 168 after surgery in the C-EPO group all significantly decreased (P ＜0.05).Conclusion C-EPO has a certain neuroprotective effect by inhibiting traumatic brain edema in the TBI rats coupled with seawater drowning,its potential mechanism might be associated with the expression of AQP4 to resist brain edema.