Abstract Currently most of antitumor pharmacology studies are performed in mice using either human xenograft or murine tumors. However, the utility of rat tumor models has not been fully explored. Some of the obvious advantages of using rats remain to be validated, for example, the easy combination of pharmacokinetic study with an efficacy study, the easy performance of animal procedures, the more options for local dosing or interventions, etc. HCCLM3 is one of the human hepatocellular carcinoma(HCC) lines that are originally derived from Chinese HCC primary tumor and well established in mouse model system over last 20 years. To realize the potential utilities of rats for tumor models, especially for the need of evaluating various local treatments for the HCC, we examined the growth and metastasis of HCCLM3 tumor following subcutaneous and orthotopic xenograft in immunodeficient rats (RNU nude rats, Charles River). Following either subcutaneous or orthotopic inoculation, HCCLM3 was able to successfully grow up with 100% take-up rate. The subcutaneous tumor grew more quickly in nude rats than in BALB/c nude mice and the tumor weight reached about 10% of body weight 28 days after inoculation. The treatment with Sutent (28mg/kg, p.o. 5 times per week) significantly inhibited the subcutaneous tumor growth by 93% (P<0.05). In comparison, the orthotopic tumor grew rather slower but showed much stronger lung metastasis potential which was not observed in nude mice in 28 days. HCCLM3 in nude rats also demonstrated the growth pattern of the single nodule growth, different from the intrahepatic dissemination and multiple nodule development in the nude mice. Our established HCCLM3 subcutaneous and orthotopic xenograft rat models provided additional useful tools for evaluation of therapeutic profile of drug candidates and different interventional strategies for the treatment of human hepatocellular carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 480.