In our studies, we found that the liver innate recognition of hepatic NK and NKT subsets was involved in murine liver injury.We established a novel NK cells-dependent murine acute hepatitis via activation Toll-like receptor3 (TLR-3) by injection of poly I:C, which may mimic the mild virus hepatitis.It was observed that there exist a network among innate immune cells such as NK cells, NKT cells and Kupffer cells in liver immune injury in our established NK cells-dependent murine model.It was noted that pretreatment with poly I : C to activate TLR-3 on Kupffer cells might pre vent against bacterial toxin (LPS)-induced fulminant hepatitis via down-regulating TLR-4 function, while TLR-3 pre-acti vation of NK cells might reduce the ConA-induced NKT cells-mediated fulminant hepatitis via blocking NKT cells recruit ment into liver.We also found that the oversensitivity to injury by immune stimulations in HBV transgenic mice correlated to over-expression of Rea 1, an NKG2D ligand of NK cells or CDld, a ligand of TCR-V&alpha14 of NKT cells, on HBV + hepatocytes, which leads to an innate immune response against hepatocytes and is critical in liver immune injury and re generation.