The parasympathetic nervous system has been known to modify innate immune responses. In animal models, acetylcholine (Ach) released from the distal ends of nerves has been shown to inhibit inflammatory responses such as endotoxic shock, pancreatitis, intestinal inflammation, etc. However, its role in LPS-induced fulminant hepatitis remains to be elucidated. Here, we demonstrate that the vagus nerve acts as a suppressor in the liver after challenge with LPS plus D-gal. The vagus nerve acts through the α7 AchR expressed on the surface of Kupffer cells, inhibiting the production of the proinflammatory cytokines TNF and IL-6. A mechanism study revealed that the suppressive effect of Ach may occur through the activation of Src kinase and subsequent inhibition of the Myd88 signal pathway. Our study has suggested a suppressive role of vagus nerve in the modulation of liver inflammatory responses, which should be noticed during clinical massive hepatectomy and liver transplantation. The nicotinic anti-inflammatory pathway may also be a potential target for sepsis after liver transplantation.