Objective To observe the preventive effect of early hormonal intervention on delayed encephalopathy after acute carbon monoxide (CO) poisoning among rats.Methods A total of 132 male Wistar rats were randomly divided into three experimental groups: CO poisoning group (COP group), CO poisoning+dexamethasone (10 mg/kg) group (DSMS-10 group), and CO poisoning + dexamethasone (30 mg/kg) group (DSMS-30 group), n=40 for each, as well as one normal control group (NC group) (n=12). The rats in experimental groups were intraperitoneally injected with CO (150 ml/kg) to establish an animal model of acute CO poisoning, while the rats in NC group were injected with an equal volume of air. The DSMS-10 group received intraperitoneal injection of dexamethasone (10 mg/kg/d) for 7 days, and the DSMS-30 group received intraperitoneal injection of dexamethasone (30 mg/kg/d) for 7 days; the treatment began within 30 min after poisoning. The control group and COP groups were injected with an equal volume of saline. At 90 min, 7 days, 14 days, and 21 days after poisoning, serum myelin basic protein (MBP) levels were measured; rats were sacrificed to collect brain tissues for HE staining and MBP immunohistochemical staining. The Morris water maze test was used to evaluate the intelligence of rats.Results The Morris water maze test showed that 8 rats in the COP group were judged to have delayed encephalopathy, 6 rats in the DSMA-10 group were judged to have delayed encephalopathy, and no cases of delayed encephalopathy were found in the DSMS-30 group and NC group. The COP group showed the most significant increase in serum MBP level, the DSMS-10 group also showed increase in serum MBP level, and the DSMS-30 group had almost normal serum MBP level; the most significant differences were seen at 90 min and 7 days after poisoning. The pathological examination showed that the rats judged to have delayed encephalopathy in the COP group had neuronal damage and MBP depigmentation in the hippocampus and subcortical region at 90 min to 21 days after poisoning; these pathological changes could be observed in all experimental groups, severest in the COP group and mildest in the DSMS-30 group.Conclusions For the rats with acute CO poisoning, dexamethasone can reduce the incidence of delayed encephalopathy when given at 10 mg/kg and can prevent delayed encephalopathy when given at 30 mg/kg.