Objective: To investigate whether CD4 CD25 regulatory T cells could regulate dendritic cells. Methods: CD4 CD25 regulatory T cells were isolated by MACS(magnetic cell sorting) from naïve BALB/ c mice. Their suppression on the proliferation of CD4 CD25 T cells was analyzed by cell proliferation assay. Autologous DCs were prepared from bone marrow progenitors and cultured with GM-CSF/IL-4. The characters of these DCs were analyzed by FACS. CD4 CD25 regulatory T cells were activated by CD3/CD28 antibodies and their cytotoxic effects on autologous DCs were evaluated in vitro by flow-based killing assay. To analyze the role of the perforin/granzyme pathway in killing, EGTA was added to inhibit calcium-dependent perform polymerization. Results: It was found that DCs derived from bone marrow expressed CD11c, MHC II and low levels of other co-stimulatory molecules such as CD80, CD86. CD4 CD25 regulatory T cells could be successfully classified by MACS with 98% purity and specifically express the Foxp3 gene. CD4 CD25 regulatory T cells stimulated by CD3/ CD28 exhibited cytotoxic effects on autologous DC targets(P < 0.05), and the process could be partially inhibited by EGTA(P < 0.05). Conclusion: CD4 CD25 regulatory T cells could regulate immune response by killing autologous DCs, and perforin/granzyme pathway might participate in this process.