Atherosclerosis (AS) is the pathological basis of common cardiovascular diseases such as heart disease and stroke, and its causative factors are complex and diverse. With the advancement of mature genetic modifications, mouse models have provided an important basis to study the pathogenesis of AS and validating drug efficacy. In this article, we review the pathological characteristics of traditional transgenic and novel mouse models on the basis of lipoprotein metabolism and histopathological changes, as well as their potential and limitations for preclinical application in drug development, so that future studies on mechanisms related to this disease can be targeted to select models.