Apelin was shown to play an important role in atherosclerosis in mice. However, the involvement of apelin in atherosclerosis in humans has not been investigated. Aims: To characterize plasma apelin levels following acute coronary syndrome (ACS) and to examine their relationship with coronary stenosis and atherosclerotic plaque stability. The study enrolled 196 patients admitted with ACS, and another 171 outpatients with no coronary heart disease as control. Plasma concentrations of apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP), and matrix metalloproteinase-9 (MMP-9) were measured 2 hours and 6 months after admission, respectively. The severity of coronary artery stenosis of ACS patients was evaluated using the Gensini score. The stability and components of atherosclerotic plaque was assessed by intravascular ultrasound (IVUS). All statistical analyses were performed using SPSS version 16.0. Apelin concentration was reduced compared with healthy controls following ACS (0.54 +/- 0.25 versus 3.22 +/- 1.08 ng/mL, P < 0.001) and remained low to 6 months. The plasma level of apelin in the ACS group was negatively correlated with the Gensini score (r = -0.382, P = 0.009). Moreover, in the ACS patients, apelin levels were significantly lower in the group with the ruptured plaque than in those with the nonruptured plaque (0.42 +/- 0.24 versus 0.68 +/- 0.30 ng/mL, P = 0.042). Apelin levels were negatively correlated with plaque cross-sectional area (CSA) (r = -0.425, P = 0.018) and positively correlated with external elastic membrane (EEM) CSA (r = 0.311, P = 0.037). Conclusions: Plasma apelin levels were inversely correlated with the severity of coronary artery stenosis and positively related with the stability of atherosclerotic plaque in humans with ACS.