We aimed to establish a rabbit model of vulnerable plaques (VPs) with the morphology and component characteristics of human VPs and to evaluate the microstructural features of VPs in vivo using intravascular optical coherence tomography (OCT). Twelve rabbits underwent endothelial denudation of the carotid artery and consumed a 1% high-cholesterol diet (HCD). They were equally divided into two groups: group A (modified needle injury) and group B (balloon injury). OCT was undertaken thrice before injury as well as 1 h and 12 weeks after injury. The degree of acute artery injury after endothelial denudation was detected by OCT. Twelve weeks after injury, OCT showed that both groups generated VPs which had thin fibrous caps and a large lipid core, whereas plaques in group A had smaller lipid arcs (P < 0.0001). Histological findings demonstrated that a larger eccentricity index (EI) (P < 0.05) and greater infiltration of macrophages (P < 0.05) in group A than in group B. Qualitative and morphometric analyses of plaques showed a significant correlation between histological and OCT measurements. A combination of modified endothelial denudation and an HCD in rabbits produced more eccentric lesions similar to those seen in humans. These data suggest that OCT could be a useful tool for evaluation of the degree of injury and VPs in vivo.