ObjectiveTo investigate the effects of MK-801 on antioxidant system activity in the central nervous system of rats with obstructive jaundice. MethodsTwenty rats were divided into four groups: sham operation group, control group, MK-801 low dose group, and MK-801 high dose group. The control group, MK-801 low dose group, and MK-801 high dose group were the obstructive jaundice model groups (OJ groups). From the first day after operation, MK-801 low dose group were processed intraperitoneal injection of MK-801 0.025 mg/(kg·d) and MK-801 high dose group were processed intraperitoneal injection of MK-801 0.25 mg/(kg·d). Meanwhile, sham operation group and control group were injected the same volume of normal saline everyday for 10 days. Three days after operation, rats' tail vein blood were collected for examining the direct bilirubin DBIL) and total bile acids (TBA) in order to determine whether the model were successfully established. And malondialdehyde (MDA), catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC) were determined on the 10th day to evaluate the oxdative status of the rats. Results①Obstructive jaundice model was established successfully.②The content of MDA in control group, MK-801 low dose group and MK-801 high dose group were significantly increased than the sham operation group, and there was statistical difference (P < 0.05). The content of MDA decreased in MK-801groups compared with the control group (P < 0.05).③Compared with the sham operation group, the activity of CAT in control group decreased significantly (P < 0.05). The activity of CAT in the MK-801 groups increased compared with the control group with significant difference (P < 0.05). There was no statistical difference on the activity of CAT between MK-801 low dose group and high dose group (P > 0.05).④Compared with sham operation group, the activity of T-SOD was decreased significantly in control group with statistical significance (P < 0.05). The activity of T-SOD were increased in the MK-801 groups compared with control group with significant difference (P < 0.05), but the activity of T-SOD was decreased significantly in the high dose group than the low dose group (P < 0.05).⑤In the Oj groups, the T-AOC were significantly increased compared with the sham operation group, and there was statistical significance (P < 0.05). The T-AOC in MK-801 groups were increased compared with the control group with statistical significance (P < 0.05), but there was no statistical difference between the MK-801 groups. Conciusions Oxidative stress exists when obstructive jaundice occurs, and obstructive jaundice can aggravate the oxidative stress damage in the rats' central nervous system and cause increasing expression of enzymes such as CAT which enhance antioxidant capacity of the whole body. MK-801 can decrease lipid peroxidation, and increase activity of CAT and SOD as well as T-AOC in CNS of jaundice rats. But High dose of MK-801 has no better effect than low dose of MK-801. On the contrary, activity of T-SOD decrease in the high dose group than in the low dose group. Further research is needed on the specific mechanism.