Renal protective effects of naringenin at 0.5, 1, and 2% of the diet in diabetic mice were examined. Naringenin supplemented at 1 and 2% increased its deposit in liver and kidney of diabetic mice. Compared with the diabetic control group, naringenin treatments at 1 and 2% lowered plasma levels of glucose and blood urea nitrogen, as well as increased insulin level and creatinine clearance (P < 0.05). Naringenin treatments dose-dependently reduced renal tumor necrosis factor-α level and expression (P < 0.05) but only at 1 and 2% significantly decreased production and expression of interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1 (P < 0.05). Naringenin intake at 2% decreased renal formation and expression of type IV collagen, fibronectin, and transforming growth factor-β1 (P < 0.05). This compound at 1 and 2% lowered protein kinase C activity and suppressed nuclear factor κB (NF-κB) p65 activity, mRNA expression, and protein production in kidney. However, this agent only at 2% diminished NF-κB p50 activity, mRNA expression, and protein production (P < 0.05). These results indicate that naringenin could attenuate diabetic nephropathy via its anti-inflammatory and antifibrotic activities.