As the main organ of human metabolism, the liver has important functions such as detoxification and bile secretion. Liver damage may lead to adverse consequences such as cirrhosis and liver failure. As the basis of liver disease research, liver injury has been widely subject to scientific research. Various chemicals are available to model liver injury with different pathogeneses. This review briefly introduces five mechanisms of animal liver injury caused by several chemical pathways, such as oxidative stress, interference of RNA synthesis, regulating enzyme activity, cholestasis induction, and promotion of tumor cell formation to provide ideas to study liver injury.