The aim of the present study was to determine whether direct visual morphology can predict vascular physiology, macrophage infiltration and plaque architecture of atherosclerotic lesions. Twenty male New Zealand white rabbits weighing 2.5-2.8 kg (mean, 2.7 +/- 0.2 kg) were used. We fed rabbits a 1% cholesterol diet after creating an injury in the middle abdominal aorta using a 2 Fr Fogarty balloon catheter. After 8 weeks, the morphology of plaque lesions was evaluated by angioscopy, and was classified as protruding or lining. Vascular endothelial function (VEF) was evaluated using a Doppler guidewire, and was expressed as ratio of basal to peak velocity (cm/s) in 30 s occlusion using a balloon catheter. Macrophages obtained from abdominal sections were stained with monoclonal antibody against rabbit macrophages (RAM-11). Density of total macrophage cell infiltration was quantified as absolute area of RAM-11 staining. Macrophage density and intima/media (I/M) ratio were significantly higher in the protruding group than in the lining group: macrophage density, 40 +/- 10 vs. 5 +/- 10%, p < 0.01; I/M ratio, 1.2 +/- 1.4 vs. 0.2 +/- 4, p < 0.05. Vascular flow reserve (VFR) was lower in the protruding group than in the lining group (1.8 +/- 0.7 vs. 2.2 +/- 0.5, p < 0.05). There was significant negative correlation between VEF and macrophage cell density (r = -0.593, p < 0.01), whereas there was no significant correlation between VEF and I/M ratio (r = -0.332, p = 0.330). The present findings suggest that protruding lesions revealed by angioscopy are rich in macrophages and have a higher I/M ratio and lower VFR.