Aim To elucidate effect of rosiglitazone (RSG) on calcification induced by advanced glycation end-products (AGE) in vivo on rat. Methods A rat model of diabetic arterial calcification (DM+VDN) was induced by streptozotocin (STZ) and high fat diet, as well as vitamin D3 and nicotine, then divided into three groups:untreated group, group treated with RSG, group treated with glibenclamide (GLB). Metabolic parameters, aortic calcium content, malondialdehyde (MDA) content, Cu/Zn superoxide dismutase (SOD) activity, receptor for advanced glycation end products (RAGE) and plasma AGE levels were measured. Results DM+VDN exhibited enhanced levels of AGE, as well as high levels of MDA and SOD. Aortas from DM+VDN exhibited high levels of calcium content. This calcification was also dramatically increased, as shown by von Kossa staining. In aorta, strong immunostaining for RAGE were observed in DM+VDN. Conversely, rosiglitazone attenuated these changes in calcium accumulation and the investigated proteins in aortas, as well as plasma AGE, MDA and SOD. Conclusion The results suggest that rosiglitazone might exert anti-calcification in partly through down-regulation of RAGE expression, thus limiting the cells’ susceptibility toward oxidative stress induced by AGE.