In adult male mice of the 129/Sv strain (genotype H-2b), behavior, macrophage activity, malondialdehyde (MDA) content, and antioxidant enzyme activity in the brain were evaluated, and changes in the above-mentioned parameters were also investigated after administration of the neurotoxin cuprizone or its combination with corticosterone. It was shown that in mice with a cuprizone diet during three weeks, the number of squares, rearings, hole-peeking, and boluses in the “open field” test was less than in intact animals (1.3, 2, 1.4, and 1.7 times, respectively). In the brains of mice with a cuprizone diet, the number and activity of macrophages (in the latex beads phagocytic test) and MDA content exceeded the values of the indicators of intact animals, and the activity of glutathione peroxidase was lower. In the mice that were administered corticosterone from eight day of the cuprizone diet (at a dose of 5 mg/kg, 14 injections), the number of squares, hole- peeking and washing became less than in animals with only the neurotoxin, while the number of macrophages (81.2 and 76%, respectively) and their activity (4.8 and 4.4 CU, respectively) in the brain were significantly higher. The brain MDA content in mice receiving a combination of neurotoxin and corticosterone exceeded the value of the indicator in the group receiving only neurotoxin, while the activity of superoxide dismutase and glutathione peroxidase was lower than in the latter group. Thus, motor, exploratory, and emotional activity in mice is suppressed by cuprizone; the number and activity of macrophages increase, as does the MDA content in the brain, while the activity of glutathione peroxidase decreases. Long-term administration of corticosterone leads to more pronounced behavioral disorders, activation of macrophages, and inhibition of antioxidant enzyme activity in the brain of mice with a cuprizone diet.