Proteomic analysis was performed in an attempt to identify a gene responsible for the expression of type 2 diabetes using a congenic rat, F.O-Nidd2/of, which possesses a single hyperglycemic QTL locus derived from the diabetic OLETF (Otsuka Long-Evans Tokushima Fatty) rat. Since the genetic difference between the congenic and its host strain, the F344 rat, is limited to the introgressed segment of 38 cM or ca. 2% of the rat whole genome, any discordant protein spots on two dimensional polyacrylamid gel electrophoresis (2D PAGE) will be considered strong candidate genes of this locus. Here we analyzed ca. one thousand protein spots in three different tissue types, liver, muscle and pancreas at 10, 20 and 30 weeks of age, we found that an acidic protein of 55 kD in muscle tissue shifts towards acidic end in an age dependent fashion in the congenic strain. However, the shift was not observed in the control rat, which is intriguing because the timing of the shift corresponds to the age at which hyperglycemia begins in the congenic. Future biochemical analysis should aid in elucidating the molecular mechanisms of glucose metabolism.