AIM Qishenkeli (QSKL), a formula composed of six herbal medicines, has long been used for the routine treatment of coronary heart disease (CHD) or chronic heart failure (CHF) in China.However, how the herbal formula work and what are their drug targets still have not well been defined.The aim of this paper is to investigate whether the effects of QSKL on CHD are associated with renin-angiotensin-aldosterone system (RAAS) and which targets are the herb acts on.METHODS The model of heart failure was produced by left coronary artery ligation with rats.Rats were randomly divided into 4 groups, the sham groups, the model group,the formula group and control group, respectively.The formula groups were lavaged with 2.33 g· kg-i QSKL (equal to the daily human dosage), taking the fosinopril sodium as control.Echocardiography was used to detect cardiac function and the extent of myocardial ischemia, the level of RAAS in myocardial tissue including renin, angiotensin Ⅱ (Ang I) and aldosterone (Ald) were examined and the expression cluster of angiotensin Ⅱ receptor 1 (AT1), angiotensin Ⅱ receptor 2 (AT2), angiotensin converting enzymes (ACE),angiotensin converting enzymes 2 (ACE2) were detected respectively to establish potential targets of QSKL.Moreover, the contents of cardiac transforming growth faction-S (TGF-β) and matrix metalloproteinase-9 (MMP-9) were also measured.RESULTS The results showed that QSKL and fosinopril sodium can both improve the ejection fraction (EF) value of the CHD, besides QSKL also decreased the left ventricular end-systolic diameter (LVEDs) and Left ventricular end-diastolic diameter (LVEDd), thus to reduce the cardiac hypertrophy degree, while fosinopril sodium had no effects on them.In RAAS pathway study, as an ACE inhibitor, fosinopril sodium down-regulated ACE expression, and eventually reduced the tissue Ang II concentration, but had no effect on ACE2.Whats more, it had no effect on renin, AT2, while QSKL can significantly decrease the level of renin and the expression of Ang Ⅱ in myocardial tissue (P<0.01).The results also revealed that QSKL can act on both AT1 and AT2 thus to block the effect of AngⅡ, and increased the level of ACE2, it also can down-regulate the levels of TGF-β and MMP-9, but has no effect on the ACE.CONCLUSION This study shows that the ameliorative effects of QSKL on CHD in rats have multi-targets associated with the inhibition of RAAS, in which renin, AT1, AT2 and ACE2 but not ACE as the drug targets to decrease the concentration of TGF-β and MMP-9, thus to produce cardio-protective therapy effects, and produce greater synergetic efficacy and fewer side effects.