<b><i>Background/Aims:</i></b> Telmisartan, an angiotensin II type 1 receptor blocker, is widely used to treat hypertension and kidney diseases, including diabetic nephropathy, because of its renoprotective effects. However, the mechanism by which telmisartan prevents proteinuria and renal dysfunction in diabetic nephropathy is still unclear. In this study, we examined the effects of telmisartan against diabetic nephropathy in <i>db/db</i> mice. <b><i>Methods:</i></b> Telmisartan was administered at a dose of 5 mg/kg/day for 3 weeks to <i>db/db</i> (diabetic) and <i>db/m</i> (control) mice. Urinary albumin excretion, renal histology, and the gene expression of oxidative stress and inflammatory markers in renal tissue were determined. To evaluate the effects of telmisartan on reactive oxygen species (ROS) production, superoxide was detected by dihydroethidium (DHE) staining in vivo and in vitro. <b><i>Results:</i></b> Telmisartan reduced albuminuria, mesangial matrix expansion, macrophage infiltration, and the expression of ROS markers (NADPH oxidase 4- and 8-hydroxydeoxyguanosine) and inflammatory cytokines (monocyte chemoattractant protein-1, osteopontin, and transforming growth factor-β) in the kidney. DHE staining showed that telmisartan decreased ROS generation in the kidney and in cultured mesangial and proximal tubular epithelial cells. <b><i>Conclusions:</i></b> Taken together, these findings indicate that telmisartan protects against diabetic nephropathy by reducing diabetes-induced oxidative stress.