Objective To investigate the relationship of formation of coronary collateral circulation(CCC) with serum levels of vessel reactive substances in patients with severe coronary arteries stenosis (SCAS). Methods A total of 80 consecutive senile patients, aged (70.23±7.86) years, who received coronary arteriography and identified with at lease 1 out of 3 main coronary arteries with over 95% stenosis in our department from June 2007 to January 2009, were subjected in this study. They were categorized into 2 groups according to their grading of collateral vessels: well-developed CCC group and proorly-developed CCC group. Vessel reactive substances, such as angiotensin-converting enzyme (ACE), angiotensin Ⅱ (Ang Ⅱ), aldosterone (ALD), endothelin (ET), and nitric oxide (NO), were measured in these patients. Results The activities or serum levels of ACE [(38.07±6.25) vs (27.02±4.15)U/L], Ang Ⅱ [(90.27±10.31) vs (70.13±7.30)ng/L], ALD [(170.75±23.46) vs (130.34±11.23)ng/L], and ET [(74.78±7.35) vs (57.23±6.04)ng/L] were significantly stronger or higher in poorly-developed CCC group than in well-developed CCC group (P＜0.05), while the level of NO was obviously lower in the poorly than the well-developed CCC group [(34.8±6.24) vs (49.34±6.67)μmol/L], P＜0.05). Conclusion The stronger activity of ACE and the higher serum levels of Ang Ⅱ, ALD, and ET are against the development of CCC in SCAS patients, but the higher level of NO is beneficial in the process.