Aim: To study whether rosiglitazone prevents the development of diabetic nephropathy through reduction of reactive oxygen species and its downstream signal transduction pathways.Methods: The rats were intraperitoneally injected with streptozotocin to induce diabetes, meanwhile the rats in the therapeutic groups were given rosiglitazone (5 or 20 mg/kg/day) for 4 weeks by intragastric administration. Blood glucose, serum lipid and creatinine, urinary albumin excretion were measured. Malondialdehyde content, the activities of nuclear factor-ĸB (NF-ĸB), antioxidant enzymes including Cu-Zn SOD and GSH-Px in kidney were also measured. In addition, the mRNA and protein expression of MCP-1 were semiquantitatively determined with PT-PCR and immunohistochemical staining respectively. Results: No significant difference of blood glucose and lipid were found between diabetic rats and rosiglitazone treatment groups. The renal histopathology was improved significantly. The expressions of MCP-1 mRNA and protein, malondialdehyde level and the activity of NF-ĸB were decreased markedly in rats treated with high-dose rosiglitazone, but the activities of renal Cu-Zn SOD and GSH-Px increased significantly. Conclusions: Rosiglitazone treatment prevented glomerular injury in diabetic rats, which was closely related with its roles of reducing reactive oxygen species, NF-ĸB activation and MCP-1 expression in the early phase of diabetic nephropathy.