Objective To explore the changes of mTOR signaling in LPS/D-gal-induced acute hepatitis in mice. Methods Twenty-six healthy adult female ICR mice were divided into two groups: the control group and experimental group, 13 mice in each group. LPS/D-gal was used to induce acute hepatitis in the mice. The survival of mice was monitored within 24 hours after LPS/D-gal challenge. At 6 hours after challenge, samples of serum and liver tissue were collected for further analysis.Results Injection of LPS/D-gal resulted in acute death of the mice within 24 hours. At 6 hours post LPS/D-gal injection, the blood levels of ALT and AST were significantly increased. The mRNA expression of inflammatory cytokines Tnfa and Il6 was up-regulated in LPS/D-gal-induced hapatitis, in which DNA fragmentation and activation of caspase-3 were subsequently observed. Immunoblot analysis showed that both mTOR pathway and NF-κB pathway were activated. Unexpectedly, inhibition of mTOR signaling could neither decrease the apoptosis in the liver nor increase the survival of mice. Conclusions The results of the present study indicate that mTOR signaling may play pleiotropic roles in the pathogenesis of LPS/D-gal-induced hepatitis.