Type 2 diabetes is a metabolic disease with a group of metabolic derangements and inflammatory reactants in the serum. Despite the substantial public health implications, markers of diabetes progression with abdominal obesity are still needed to facilitate early detection and treatment. In this study, we performed a proteomic approach to identify differential target proteins underlying diabetes progression in patients with abdominal obesity. Proteomic differences were investigated in the serum of controls and patients with prediabetes or diabetes with or without abdominal obesity by 2-DE combined with MALDI-TOF-MS. Proteomics data were validated by western blot analyses and major protein-protein interactions were assessed using a network analysis with String database. Among 245 matched protein spots, 36 exhibited marked differences in normal patients with abdominal obesity, prediabetes, and diabetes compared to levels in normal patients without abdominal obesity. Seven (Alpha-1-antichymotrypsin, Alpha-1-antitrypsin, Apolipoprotein A-I, haptoglobin, retinol-binding protein 4, transthyretin, and zinc-alpha2-glycoprotein) of these spots exhibited significant differences between normal and prediabetes/diabetes patients. After a network analysis, functional annotation using Gene Ontology indicated that most of the identified proteins were involved in lipid transport, lipid localization, and the regulation of serum lipoprotein particle levels. Our results indicated that variation in the levels of these identified protein biomarkers has been reported in normal, prediabetes and diabetic Assessment of the levels of these biomarkers may contribute to the development of biomarkers for not only early diagnosis but also in prognosis of diabetes mellitus type 2.