Objective To investigate the changes in natural killer (NK) cells and natural killer dendritic cells (NKDCs) during immune system rebuilding, and explore the correlation between NKDCs and NK cells. Methods A mouse model of bone marrow reconstruction was used, and NK cells, dendritic cells (DCs) and NKDCs were sorted with flow cytometry. NK cells and NKDCs were stimulated with the immunologic adjuvant CpG in vitro, and the secretion of cytokine IFN-γ was detected. Results In the process of rebuilding the immune system, the numbers of both NK cells and NKDCs in bone marrow or spleen increased within one week, and returned to normal at week 4, suggesting that innate immune function was rebuilt first in bone marrow rebuilding. NK cells and NKDCs were functionally different. NKDCs produced more IFN-γ as compared with NK cells. CpG stimulated NKDCs to produce IFN-γ, but it was not the case for NK cells. INF-γ production was not associated with B220 expression in NK cells or NKDCs. Conclusion NKDCs may play a key role in the innate anti-tumor immunity.