Diabetes mellitus (DM) is now a global health problem, however, its pathogenesis has not yet been fully deciphered. Even though modern medicine has great contribution to the control and treatment of DM, it is still far from success to completely cure the disease. Panax ginseng C.A. Meyer (ginseng) is a well-recognized traditional Chinese medicine for treating DM in Asia. In this study, high throughput proteomic approach has been adopted to investigate the antidiabetic action of 2 weeks' ginsenoside Re (Re, a major component of ginseng) administration to streptozotocin-induced diabetic rats. Employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and bioinformatics, 432 cluster peaks were detected in the samples, among them 293 potential biomarkers were found to have significant differentiations between the DM and control normal rats. When the Re-treated diabetic rats were compared to the untreated ones, a protein peak was detected to have significant alteration corresponding to Re treatment. This specific protein was found to match with C-reactive protein (CRP) in the protein database, and was subsequently validated by ELISA. This is the first study demonstrated that CRP could be altered by Re treatment, indicating that Re may improve diabetes and its complications by alleviation of inflammation.