HMG-CoA reductase inhibitors (statins) have been shown to improve the endothelial function by lowering lipids. Recent studies also suggest a direct impact of statins on the vascular wall. We assessed the rapid effect of cerivastatin on the coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). The coronary flow velocity from the distal left anterior descending artery was measured in 16 healthy subjects (all male, age 24–38 years) using a 5-MHz transducer, on the day before, just before, and 3 h after administering 0.3 mg of cerivastatin. Hyperemia was achieved by the intravenous administration of adenosine, and the CFVR was calculated as the radio of the mean diastolic hyperemic coronary flow velocity to the basal flow velocity. The serum lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured. The CFVR following the single administration of cerivastatin increased from 2.93 ± 0.58 to 3.91 ± 0.86, P = 0.003, and was significantly higher than the CFVR measured at the same time on the previous day (3.91 ± 0.86 vs 3.37 ± 0.48, P = 0.009). Neither the serum lipid profile nor hsCRP exhibited a remarkable change after cerivastatin administration. We concluded that a single-dose administration of cerivastatin, an HMG-CoA reductase inhibitor, improves the coronary flow velocity reserve without modifying the serum lipid profile.