Possible clinical diagnosis biomarkers of diabetes were proposed using proteomics and bioinformatics methods through the preliminary study on the formaldehyde-human serum albumin crosslinkage. Using LC/MS techniques, the experiment on in vivo cross-linking reaction of formaldehyde with pure protein or plasma protein revealed that the cross-linking reaction of human serum albumin and forrmaldehyde would occur and the concentrations of some normal peptides would change. A group of significant peptides of human serum albumin were selected. As the results of in vivo cross-linking reaction, Non-enzymatic glycosylation modification of HSA were observed in diabetic. The same change of the concentrations of some peptides happened. The above-mentioned results were demonstrated with the hematoplasmas of normal people and diabetics.