We studied the prevention of a mice model of rheumatoid arthritis, the collagen-induced arthritis (CIA) model, with DNA-matured dendritic cell injection and then studied the induction of Treg through this innate immunity stimulation. CIA was induced as described in DBA/1 mice with bovine type II collagen intradermal injections. Intermediate DNA-matured dendritic cells were injected at D14 intraperitoneally. The clinical course of arthritis was followed and B-cell and T-cell responses were assayed. The induction of CD4+CD25+ was tested by flow cytometry and the induction of Treg markers was quantified by quantitative RT-PCR. Treatment of CIA with intermediate DNA-matured dendritic cells could prevent arthritis as well as lipopolysaccharide-matured dendritic cells. Neither B-cell and T-cell responses were not modified nor was a TH2 response observed. The induction of Treg (CD4+CD25+) cells was observed in blood, and lymph nodes. The induction of foxp3 could be quantified and increased with DNA-matured dendritic cells in peripheral nodes. In conclusion we observed a prevention of CIA with the injection of DNA-matured dendritic cells that did not modify the specific response against bovine type II collagen. Because of the absence of T-cell and B-cell response modification as well as TH2 modification, we believed that the induction of CD4+CD25+ cells that expressed foxp3 are involved in the prevention of CIA we observed.