Abstract: AIM:To assess the diagnostic value of two-dimensional ultrasound and optical coherence tomography (OCT) for early-stage atherosclerosis on experimental rabbit carotid artery atherosclerotic model. METHODS: Forty New Zealand white rabbits were fed with a high-fat diet for 2 weeks before balloon injury and then were given a high-fat diet for another 4 weeks. At week 6, the right common carotid artery was scanned by two-dimensional ultrasound followed by OCT examination. The rabbits were then sacrificed and their arteries were fixed for serial hematoxylin-eosin staining. Macrophage content was semiquantified by immunostaining of CD68 antigen-antibody reaction. RESULTS: Histopathology confirmed that 17 (43%) rabbits had type III lesions. OCT showed atherosclerosis plaque formation in 15 rabbits and two-dimensional ultrasound showed intima thickening in only seven rabbits (positive rate: 88% vs. 41%, P<0.01). Histopathology confirmed that eight (20%) rabbits had type II lesions and 13 (33%) rabbits had type I lesions. OCT showed type II lesions in five rabbits, whereas two-dimensional ultrasound showed no abnormal changes in vascular walls (positive rate: 62% vs. 0, P<0.05). OCT showed type I lesions in five rabbits, whereas two-dimensional ultrasound showed no abnormal changes in vascular walls (positive rate: 38% vs. 0%, P<0.05). CONCLUSION: Both two-dimensional ultrasound and OCT demonstrate some diagnostic value for early-stage atherosclerosis, but OCT can provide a much more precise intravascular atherosclerosis image of early-stage atherosclerosis.