In this study, we characterized the therapeutical effects of Salviae Mitiorrhizae (Danshen) and Cortex Moutan (Danpi) extract (SDD) on Sprague-Dawley rats subjected to coronary artery ligation, and applied proteomic approach to investigate its potential mechanism of action. The chemical composition of SDD was investigated by HPLC/MS(n) analysis. Measurement for serum levels of creatine kinase (CK), creatine kinase-MB (CK-MB), nitrite and histological study for infarct area of heart were performed. Moreover, protein abundance profiles of myocardium were compared by two-dimensional gel electrophoresis and altered proteins were identified by MALDI-TOF-MS. The results showed SDD significantly decreased CK, CK-MB concentration in serum and infarct area of heart, while increased the release of nitrite in rats with coronary occlusion. Increased concentration of ATP and total adenine nucleotide indicated the energy metabolism has been improved in ischemic heart induced by SDD. Proteomic data revealed that 23 proteins associated with energy metabolism, oxidative stress and cytoskeleton were modulated in SDD treated rats.