Chronic liver disease can further develop to liver fibrosis and cirrhosis. Currently, there is no effective treatment except liver orthotopic transplantation at this point. The extreme shortage of liver organ forced people to find alternative treatment strategies. Mesenchymal stem cells (MSCs) have the abilities of immunomodulatory, hepatocyte differentiation, promotion of liver cells regeneration in situ and inhibiting the activation of hepatic stellate cells. Therefore, MSCs transplantation provides a very broad prospect for cell therapy. It is important to provide preclinical evaluation of the efficacy and safety before the application of cell therapy in clinic trials. The progress of various animal models of human liver disease and significance of using MSCs to treat liver diseases in preclincal studies based on these animal models were reviewed in this paper.