Diabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes. Recent cardiology studies suggest that spermine has cardioprotective effect. Here, we used proteomics analyses to reveal the underlying research target in type 2 diabetic mouse model treated with spermine. Left ventricular tissue was excised from 9 mice (Control group, 3; T2D group(db/db mouse), 3; T2D+SP group, 3) and analyzed. Quantitative analysis of the global proteome were detected using 4D label-free technique,and differentially expressed proteins (DEPs) were used to perform bioinformatic analyses.