Taken together, the present study found that AMPK was activated in mice with LPS/D-Gal-induced fulminant hepatitis and the activated AMPK promoted hepatocyte apoptosis via phosphorylating JNK at the late stage after LPS/D-Gal challenge, while inhibition of AMPK resulted in suppressed apoptosis and alleviated liver injury. This evidence concerns the gene MAPK8 and Fulminant hepatitis.