During the incubation of purified α-synuclein with fructose or glucose, it was observed that the protein intrinsic fluorescence at 308 nm decreased while the fluorescence of glycated derivant at 447 nm increased. This fluorescence representing nonenzymatic glycation of α-synuclein was more rapidly formed in the presence of fructose than that of glucose. Interestingly, an energy transfer could be observed from the intrinsic fluorescence to the nonenzymatic glycating fluorescence, suggesting a near distance between Tyr residues and the nonenzymatic glycated derivant. Experiments using circular dichroism showed that the content of α-helix of nonenzymatic glycated α-synuclein was increased during the nonenzymatic glycation, especially incubated with fructose. The nonenzymatic glycated α-synuclein was in some rod-like filaments under the electronic microscope. That is to say, nonenzymatic glycation induces the conformational changes of α-synuclein which is more vulnerable to the nonenzymatic glycation of fructose. It appears that nonenzymatic glycation induces α-synuclein misfolding and probably aggregation in cell.