Homeostasis-driven proliferation of T cells is an important means of reconstituting T-cell-dependent immunity after lymphodepletion regimens, such as chemotherapy or radiotherapy. Immune-reconstituted mice that receive a tumor vaccine mount more efficient anti-tumor immune responses compared with control mice. In the present study, we evaluated the anti-tumor immune responses in immune-reconstituted mice vaccinated with inactivated leukemia cells and explored the mechanisms underlying these immune responses. Test C57BL/6 mice were lymphodepleted by irradiation and immune-reconstituted with naïve mouse spleen lymphocytes. Mice were then injected with an inactivated FBL-3 tumor cell vaccine and challenged with FBL-3 tumor cells. Anti-tumor responses were evaluated by determining the rate of tumor formation, latency, tumor size, interferon gamma levels, and macrophage and CTL cytotoxicities. When challenged with tumor cells, immune-reconstituted, vaccinated mice exhibited a significantly lower mortality, smaller average tumor volume, and a significantly longer mean survival time. They had more robust cellular immunity, reflected by higher levels of INF-γ production and higher macrophage- and CTL-mediated cytotoxicities. Our results suggest that immune reconstitution enhanced the anti-tumor immune responses in mice injected with a tumor vaccine via generation of CTLs. These results have important implications for immunotherapy used for leukemia.