Background: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the industrialized world. Optical coherence tomography (OCT) is a high-resolution intravascular imaging technology with a potential for in vivo plaque characterization. Although structural remodeling of the arterial vessel wall during plaque development can change tissue optical scattering properties, very limited evidence is available on the exact optical scattering properties of plaques. The scattering coefficient, mu(s), and the anisotropy factor, g, can be derived from OCT images by fitting a theoretical model to individual depth-scans. The aim of the current study was to use this method to examine by OCT the scattering properties of human arteries with different stages of atherosclerotic lesion development. Methods: Normal (n=4), lipid-rich (n=4), and fibrous (n=3) aortic blocks as classified by parallel histopathologic examination were obtained within 24 hours of death and imaged by OCT. The intima was located in the OCT images, and then further split into 115 blocks (41 normal, 40 lipid-rich, and 34 fibrous) of adjacent OCT depth-scans transversely spanning similar to200-300 mum. Scattering signals from each block were averaged and fit to the theoretical model. From these fittings, lit, and g were extracted. Results and Discussion: The optical scattering proper-ties of normal aortic intima were quite different from lipid-rich and fibrous lesions, respectively. We discovered that the normal intima was generally highly forward scattering, i.e., with 0.917<g<1.00, while diseased vessels were much less so. Furthermore, normal vessels usually had 15<mu(s)<39 mm(-1), whereas lipid-rich blocks had mu(s)<15 mm(-1). Fibrous blocks displayed large variations in mu(s), reflecting a histopathology with varying amounts of collagen, lipids, and elastin. Based on our findings, we defined a criteria of g, and g for normal intimas, using the above values of mu(s) and g as cutoffs. Our "normal" criteria demonstrated high sensitivity (92.4%) and specificity (82.4%). We conclude, that a detailed analysis of the tissue optical scattering properties can enhance the capacity of OCT to provide information about vascular pathology.