Abstract: Objective To analysis serum protein group in patients with type 2 diabetes with macrovascular complication by application of combination of weak cation exchange (WCX) beads and Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS),to screen the differential protein peaks and establish the decision tree model; and to explore the clinical significance of the decision tree model in early diagnosis of type 2 diabetes with macrovascular complication.Methods This study included 55 patients with type 2 diabetes with macrovascular complication, 84 type 2 diabetic patients without macrovascular complication. Weak cation exchange beads (WCX) combined with MALDI-TOF-MS technique was employed to analyze the serum proteomics. The differential protein peaks were selected to build the decision tree model, and the reliability of the model was verified by blind test after the sample size was expanded.Results Several protein peaks were identified to be strongly correlated with incidence of macrovascular complication in type 2 diabetic patients. In those proteins, three diagnostic markers, i.e.16 062.20 (m/z),31 883.60 (m/z),7 986.76 (m/z) were selected to differentiate those with macrovascular complication or not. Further blind test showed that the sensitivity and specificity of the combined markers were 96.3% and 100%, respectively.Conclusion With the technique of WCX beads combined with MALDI-TOF-MS,several specific protein peaks correlated with the incidence of macrovascular complications in type 2 diabetic patients is successfully identified. These protein peaks might serve as biomarkers for the prognosis of macrovascular complications.