In the human body, the largest gland is the liver and does a lot of essential work of the body. Liver damage is the cause of mortality and increasing day by day. Liver disease is caused by multiple factors, such as an autoimmune condition, toxic chemical exposure, viral infection, and dietary factors. Drug-induced liver injury (DILI) is a critical issue in drug development because DILI causes failures in clinical trials and the withdrawal of approved drugs from the market and leading to pathological changes result, including increase in SGOT, SGPT and bilirubin as well as the free radical generation. In this review, contains the animal model of hepatotoxicity with a different cause, their action mech., and procedure with dose. These models include the toxicity caused by chemical, drug, radiation, metal, diet, and high-fat this will lead to pathological changes resulting in hepatotoxicity.