Arginine (Arg) is known to possess numerous useful physiological properties and have immunomodulatory effects. In vitro studies reported that Arg inhibits advanced glycation endproduct (AGE) formation; however, the effects of Arg on the receptor of AGE (RAGE) expression in inflammatory conditions are not clear. The present study investigated the effects of dietary Arg supplementation on inflammatory mediator production and RAGE expression in type 2 diabetic rats. There were one normal control (NC) group and two diabetic groups in the present study. Rats in the NC group were fed with a regular chow diet. One diabetic group (DM) was fed a common semi-purified diet while the other diabetic group received a diet in which part of the casein was replaced by Arg (DM-Arg) for 8 weeks. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin. Rats with blood glucose levels exceeding 1800 mg/l were considered diabetic. Blood samples and the liver and lungs of the animals were collected at the end of the study for further analysis. Results showed that plasma glucose and fructosamine contents were significantly higher in the diabetic groups than those in the NC group. The DM group had higher fructosamine and C-reactive protein than the DM-Arg group. Immunohistochemical staining showed that the expressions of RAGE in liver and lung tissues were significantly lower in the DM-Arg group than in the DM group. These results suggest that supplemental dietary Arg can decrease AGE-RAGE interactions and consequently reduce tissue damage in rats with type 2 diabetes.