Objective To compare the livers of four commonly used laboratory animals (mouse, rat, guinea pig, and rabbit) with the human liver regarding tissue morphology, in order to provide a reference for study of the liver and the choice of laboratory animal. Methods Livers of normal mice, rats, guinea pigs, and rabbits were obtained. The morphology, hepatic lobules, organ coefficient, and nucleoplasm ratio of the livers of the four animals were investigated and compared with those of human. Results The results showed that the morphological characteristics of rabbit liver were the most similar to those of human liver, and the shapes of rabbit liver and human liver were irregular wedge and wedge, respectively. The nucleoplasm ratio of rabbit was also the closest to that of human, at 0. 158 and 0. 149, respectively. The hepatic lobules of guinea pig were the closest to those of human, with both five lobules. The liver coefficient of guinea pig was also the closest to that of human, at 3. 096% and 2. 35%, respectively. Conclusions The organization and morphological characteristics of the liver of rabbit and guinea pig are closest to human, so these two animals may be more suitable for liver?related research.