As a major complication of diabetes, diabetic nephropathy (DN) has become a major cause for end stage renal failure. Increasing evidences demonstrated that DN is a kind of inflammation disease. However, the exact mechanism is not completely elucidated. In an effort to investigate the possible role of C3aR in the development of DN, it was found unexpectedly a kind of C3aR highly expressing infiltrates in the renal tissue of patients with DN. To identify the cells and evaluate the possible role of the cells in the development of DN, forty five cases of patients with DN were selected and sections of their renal biopsy were analyzed by histological, immunohistochemical, double immunofluorescence labeling, immunoelectronicmicroscopic methods and toluidine blue staining while another 15 sections of renal biopsy from normal transplantation donor were used as normal controls. The number of C3aR highly positive cells in each section was counted and the density of the cell was calculated, and the correlation between the density of the cell and the development of DN was analyzed. Light microscopic and electron-microscopic analysis revealed that the cells were similar morphologically to mast cell. Double immunofluorescence labeling analysis demonstrated that the cells were positive in CD68 and tryptase staining while negative in CD45 staining, which is also in accordance with that of mast cells. Toluidine blue staining analysis further proved that the cells were a kind of mast cells. Only very small number of the C3aR highly positive mast cells was found in the renal biopsy of normal control group. However, the number of the cells increased with the development of DN, and correlated linearly with the urine protein level and serum creatinine. These results strongly suggested that mast cells are involved in the development of DN. C3aR might play an important role in the recruitment and activation of renal mast cell and thus contribute to the development of DN.