Comparative quantitation has become an increasingly desirable tool in determining compositional differences of aortic plaque lesion in transgenically altered mice. To this end, methodology has been developed to identify lipid, cellularity, collagen, and elastin components using traditional bright-field microscopy, fluorescence, and polarized light microscopy, employing both confocal and wide-field imaging systems. Subsequent imaging processing and analysis on the digitally captured images reveals differences in compositional components as influenced by diet, age, and gender. This method can be expanded to employ a rich variety of histochemical and immunohistochemical staining protocols.