C3aR is a receptor of anaphylatoxin C3a and have been reported associated with inflammation disease. Kidney samples were obtained from db/db mice and their db/m littermates at the age of 4, 8, 12, 16 and 20 weeks. The expression of C3aR was assessed by RT-PCR, Western blotting and immunohistochemistry, and then correlated with biochemical and histological indices of kidney injury. No significant difference of C3aR expression was found in the kidney of db/db mice as compared with the control db/m mice at the age of 4 weeks, a time when all biochemical and histological indices indicated that the mice were in pre-diabetic condition. However, with the development of obesity, hyperglycemia and proteinuria, the renal expression of C3aR in the db/db mice increased as compared with the db/m mice of the same age. Immunohistochemistry analysis revealed that C3aR protein distributed specifically in renal epithelial cells, including tubular epithelial cells, glomerular podocytes and parietal epithelial cells both in db/m and db/db mice. Much more intensity of C3aR immunohistochemical staining was found in the epithelial cells of proximal tubule which just located at the intermedial of cortex and medulla. In the glomerulus, C3aR was found distributed specifically in the podocytes position and no C3aR staining was found in the mesangial and endothelial cells. In diabetic db/db mice, the increased expression of C3aR was found mainly in proximal tubule and podocytes. Interestingly, serious vacuolar degeneration was often observed in tubular cells with higher intenstity of C3aR immunohistochemical staining. All these suggested that C3aR might have something to do with the initiation or/and development of diabetic nephropathy, especially in the pathogenesis of tubular cells and podocytes.