It is well known that both atherosclerosis initiated by endothelial dysfunction due to inflammatory cascade and coronary flow reserve (CFR) are useful in the functional or risk assessment of coronary microcirculation. The aim of this study is to elucidate the association between early atherosclerotic inflammatory markers and CFR using transthoracic echocardiography (TTE) in subjects with cardiac syndrome X. A total of 135 individuals (mean age 56 ± 9 years, 79 males and 56 females) with angina or angina-like chest pain and a normal coronary angiogram were enrolled. The early inflammatory biomarkers related to atherosclerosis, namely soluble vascular adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and lipoprotein-associated phospholipase A2 (Lp-PLA2), were compared with analyzed CFR, using TTE and adenosine or dipyridamole, measured within 2 weeks after coronary angiography. There was an inverse correlation between sVCAM-1 and CFR (r = -0.225, P = 0.014). In the two groups divided by a CFR of 2.0, sVCAM-1 was significantly higher in the group with CFR <2.0 than in the group with CFR ≥2.0 (n = 21: 757 ± 323 ng/ml, vs n = 114: 628 ± 146 ng/ml, P = 0.007). In multivariate analysis, sVCAM-1 was an independent factor related to a CFR <2.0 (odds ratio 1.003, 95 % confidence interval 1.001-1.006, P = 0.023). Our results showed that sVCAM-1 levels were inversely associated with CFR using TTE in cardiac syndrome X. Further studies are warranted to validate whether increased sVCAM-1 concentration, as an inflammatory modulator, is reflected in the presence of subclinical coronary atherosclerosis.