Objective：To explore whether the cell cycle checkpoint kinase 2（cell-cycle checkpoint kinase 2，Chk2）knockout could alleviate the brain aging phenotype of B cell-specific MLV integration site-1（B cell-specific MLV integration site-1，Bmi-1）deficiency mice. Methods：The two-month-old of Bmi-1 gene knockout（Bmi-1-/-）mice，Chk2 gene knockout（Chk2-/-）mice，Bmi-1 and Chk2 double knockout（Bmi-1-/-Chk2-/-）mice and wild type（wild type，WT）littermates were used in this study. The expression of NeuN，GFAP，Iba1 and p16 in the cerebral cortex，hippocampus and hypothalamus of the above four groups of mice were detected by immunohistochemical staining. The expression of p16，SOD1 and SOD2 protein in the cerebral cortex of the above four groups were analyzed by Western blot. Results：Compared with the WT littermates，the percentages of NeuN and Iba1 positive cells in the above brain regions were significantly decreased，the percentage of GFAP and p16 positive cells were significantly increased，the protein expression levels of SOD1 and SOD2 were significantly decreased，and the protein expression levels of p16 were significantly increased in the Bmi-1-/- mice. However，in Chk2-/- mice，the percentages of NeuN and Iba1 positive cells were increased，the percentage of GFAP and p16 positive cells were significantly decreased，the protein expressions of SOD1 and SOD2 were significantly increased，and the protein expression of p16 were significantly decreased. Compared with the Bmi-1-/- mice，Chk2 knockout increased the percentage of NeuN and Iba1 positive cells in the above brain regions，decreased the percentage of GFAP and p16 positive cells，increased the protein expressions of SOD1 and SOD2，and decreased the protein expressions of p16 in the Bmi-1-/-Chk2-/- mice significantly. Conclusion：Chk2 knockout can attenuate the brain aging phenotype induced by Bmi-1 deficiency in mice by enhancing the antioxidant capacity.