Trichosanthes pericarpium (TP) had been widely used to cure patients of cardiovascular disease for 2,000 years in China. This study aims to extend our previous work to explore the mechanism underlying the protective effect of TP on acute myocardial ischemia (AMI). We hypothesized that TP may display its protective effect on AMI by promoting the mobilization of endothelial progenitor cells (EPC) via up-regulating the expression level of vascular endothelial growth factor (VEGF), endothelial nitric oxide syntheses (eNOS), nitric oxide (NO), and matrix metalloproteinase 9 (MMP-9) in AMI rats. To confirm this hypothesis, we treated AMI model rats with intragastrical administration of TP aqueous extract (TPAE), and examined both changes in the number of CEPC, and the expression levels of VEGF, eNOS, NO, and MMP-9 in myocardial tissue and their plasma content in these rats. Rats in each group were randomly divided into seven subgroups. From day 1 to 7 following AMI modeling, rats in these subgroups was sequentially phlebotomized from their celiac artery after being anesthetized by chloral hydrate. We found that, compared with the AMI model rats, in rats treated by TPAE, the CEPC counts, the expression of VEGF, eNOS, NO, and MMP-9 in myocardial tissue and their plasma content all increased more rapidly 7 days after AMI and remained at higher level (P < 0.05 or P < 0.01). Our results showed that, in AMI rats, the TPAE could significantly promote the mobilization of EPC and up-regulate the expression level of VEGF, eNOS, NO, and MMP-9 in myocardium and their plasma content. Therefore, our results suggest that TAPE may regulate EPC mobilization through up-regulating the expression level of VEGF, eNOS, NO and MMP-9 in the myocardium of AMI rats.