ABSTRACT: Bariatric surgery restores glucose tolerance in many, but not all, severely obese subjects with type 2 diabetes (T2D). We aimed to evaluate the plasma protein profiles associated with the T2D remission after obesity surgery. We recruited seventeen women with severe obesity submitted to bariatric procedures, including six non-diabetic patients and eleven patients with T2D. After surgery, diabetes remitted in 7 of the 11 patients with T2D. Plasma protein profiles at baseline and 6 months after bariatric surgery were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight coupled to mass spectrometry (MALDI-TOF/TOF MS). Remission of T2D following bariatric procedures was associated with changes in alpha-1-antichymotrypsin (SERPINA 3, p < 0.05), alpha-2-macroglobulin (A2M, p < 0.005), ceruloplasmin (CP, p < 0.05), fibrinogen beta chain (FBG, p < 0.05), fibrinogen gamma chain (FGG, p < 0.05), gelsolin (GSN, p < 0.05), prothrombin (F2, p < 0.05), and serum amyloid p-component (APCS, p < 0.05). The resolution of diabetes after bariatric surgery is associated with specific changes in the plasma proteomic profiles of proteins involved in acute-phase response, fibrinolysis, platelet degranulation, and blood coagulation, providing a pathophysiological basis for the study of their potential use as biomarkers of the surgical remission of T2D in a larger series of severely obese patients.