Myocardial ischemia (MI) is a worldwide epidemic. Compound Danshen Tablets (CDTs), an herbal compound preparation, are widely used to treat MI in China. In this study, we aimed to explore novel biomarkers to increase the understanding of MI and investigate therapeutic mechanisms of CDT by using a metabolomic approach. Plasma extracts from sham, MI model, CDT- and western medicines (isosorbide dinitrate, verapamil, propranolol, captopril, and trimethazine)-treated rats were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The orthogonal partial least square (OPLS) model was built to find metabolites expressed in significantly different amounts between MI and sham rats. Meanwhile, partial least squares discriminant analysis (PLS-DA) was used to investigate CDT's protective effects. The results showed that CDT presented protective effects on MI by reversing potential biomarkers to sham levels, especially for the four metabolites in the pathway of purine metabolism (hypoxanthine, xanthine, inosine and allantoin).