Aim To investigate the role of apolipoprotein E （ApoE） on the migration, proliferation, and differentiation of CD11b⁺Gr-1⁺ immature myeloid cells with ApoE genetic deficiency mice. Methods CD11b⁺Gr-1⁺ myeloid cells, CD11b⁺Gr-1^- monocytes, and CD11b^-Gr-1⁺ granulocytes in the peripheral blood, spleen, and bone marrow of ApoE^－/－ mice and control C57/B6 mice were analyzed by flow cytometry. Expression of ApoE in CD11b⁺ myeloid cells were examined by quantitative RT-PCR and immune-fluorescence co-staining with anti-CD11b and anti-ApoE. Cell cycle analysis was performed by flow cytometry. Results （1） Genetic deficiency of ApoE markedly promoted the migration of multiple myeloid subsets, in particular CD11b⁺Gr-1⁺ myeloid cells and CD11b⁺Gr-1^- monocytes. （2） Genetic deficiency of ApoE significantly increased the percentage of CD11b⁺Gr-1⁺ immature myeloid cells in the spleen and bone marrow of ApoE^－/－ mice compared with wild type mice. （3） ApoE was highly expressed in CD11b⁺ myeloid cells located in the spleen and bone marrow. （4） ApoE deficiency increased the percentage of CD11b⁺Gr-1⁺ myeloid cells in S cell cycle. Conclusions ApoE deficiency significantly promotes the proliferation, differentiation, and migration of CD11b⁺Gr-1⁺ immature myeloid cells in the spleen and bone marrow of ApoE^－/－ mice. Repressing the proliferation of CD11b⁺Gr-1⁺ immature myeloid cells and macrophage differentiation through an ApoE dependent signal pathway may provide a novel sight on the treatment of atherosclerosis.