Comparative anatomy is the study of similarities and differences in the anatomy of different organisms. It is closely related to evolutionary biology and phylogeny. This research work is aimed at making comparisms between two animals constantly in use in research primarily as models for various human medical conditions and even for production of antibodies for vaccines. The study is aimed at finding the differences and similarities of the guinea pig and wistar rat liver. Guinea pigs and wistar rats are currently in use in laboratory research as models for various human medical conditions, for virology and toxicological studies just to mention a few. In this study a total number of 5 Guinea pigs and 5 Wistar rats all adult males were used. The mean body weights of the Guinea pigs were 481.4g and 90.80g for the wistar rat. The mean weight for the liver was 17.80g for the Guinea pig and 6.80g for the wistar rat. The mean length of the liver was 5.22cm for the Guinea pig and 1.88 cm for the wistar rat. A gross physical examination of the liver was carried out, the colour, texture, and number of lobes were observed and recorded. Histological study was done using routine (H and E staining) histological techniques. Findings are: Basic histology of the guinea pig and wistar rat liver are similar. Comparatively, the liver of the Guinea pig and Wistar rat studied showed that they are phylogenetically related. Histologically, liver of the experimental animals studied showed basic similar histo-architecture.