Abstract: Objective To investigate the expression and significance of phosphorylated p38mitogen- activated protein kinase( p- p38MAPK)in mice with acute liver failure induced by D- galactosamine( D- Gal N) / lipopolysaccharide( LPS) and patients with HBV- related acute-on- chronic liver failure( HBV- ACLF). Methods C57 BL /6 mice induced by D- Gal N / LPS were used to establish an acute liver failure model,and experimental groups were set up at 0,0. 5,1,2,4,6,and 8 hours( n = 4 for each group). All mice were sacrificed and the samples of liver tissues were given HE staining to observe pathological changes. Western blotting and immunohistochemical staining were used to perform semiquantitative analysis and detect the expression of p- p38 MAPK in liver tissues. Meanwhile,the expression of p-p38 MAPK in patients with HBV- ACLF,hepatitis B cirrhosis,and chronic hepatitis B was also observed. Independent- samples t test was used to draw comparison between groups. Results Western blotting showed that the expression of p- p38 MAPK in liver tissue homogenate increased with time. The semiquantitative analysis showed that the expression was significantly higher in the 6 h group than in the control group( t =- 2. 727,P = 0. 034). Immunohistochemical staining showed that liver inflammation aggravated with the survival time,and p-p38 MAPK was expressed by sinus cells at early stage,and then by liver cells with the damage continued in mice,and there were lots of p-p38MAPK- positive liver cells around the necrotic liver tissues. Expression of p- p38 MAPK was very low in normal human liver tissues; however,tumor- infiltrating lymphocytes and p- p38MAPK- positive liver cells could be seen in liver tissues of patients with chronic hepatitis B. The expression of p- p38 MAPK was increasingly observed with the course of the disease,which was consistent with the aggravation of the disease. Conclusion The expression of p- p38 MAPK is found positively correlated with the liver tissue damage in the mouse model of acute liver failure induced by D- Gal N / LPS,implying that p- p38 MAPK plays a significant role in the development of acute hepatic failure. In HBV- ACLF patients,the p- p38 MAPK signaling pathway may play a critical role in the development of liver failure.