Abstract: Objective: To observe the changes of plasma high mobility group protein -1 (HMGB-1) in rabbits after acute CO poisoning dynamically,discuss the association between HMGB-1 and delayed neuropsychological sequelae,and to analyze its possible mechanism in the course of the disease. Methods: Twenty-four healthy rabbits were randomly divided into control group,delayed neuropsychological sequelae after acute CO poisoning group (model group),and sodium butyrate pretreatment group (intervention group),8 in each. The rabbits were injected continuously interval high purity CO gas intraperitoneally to prepare the model of delayed neuropsychological sequelae after acute CO poisoning. After the end of modeling,1,3,6,12,24 h,and 3,7,14,21 d,blood was drawn from ear vein each time to test the levels of HMGB-1. Results: The plasma HMGB-1 levels at 3 h after the end of modeling in model group had statistical difference in contrast to control group (P < 0.05). From 6 h to 21 d after the end of modeling,the differences between model group and control group were all significance (P < 0.01),while were not statistical difference between intervention group and control group (P > 0.05); from 6 h to 21 d,in poisoned rabbits (model group and intervention group),the rate of delayed encephalopathy was significant difference compared to no encephalopathy happening (P < 0.01). Conclusions: Early plasma HMGB-1 levels are highly correlated with delayed neuropsychological sequelae after acute CO poisoning, and HMGB-1 can play a crucial role in the formation of delayed encephalopathy.