We examined the role of fructose in the development of diabetic complications. Compared with glucose, fructose increased the fluorescence intensity and the cross-linking of glycated collagen, and promoted the polymerization of proteins. Therefore fructose accelerated the production of advanced glycation end-products more than glucose. In addition, fructose enhanced the reactive oxygen or oxygen radical generation and the associated degeneration of proteins and lipids. These actions of fructose appeared to be due to the formation of dicarbonyl compounds such as 3-deoxyglucosone, a highly reactive intermediate product formed in the advanced glycation stage. These results suggest that fructose is closely involved not only in glycation but also in the polyol pathway and peroxidation reactions through free radical formation. Thus, fructose is considered to be a more critical reducing sugar associated with the progression of diabetic complications than it has been thought until now.