Objective To investigate the role and mechanism of NOD2 ( nucleotide-binding oligomerization domain 2, NOD2), a pattern recognition receptor in liver cells, in the process of liver inflammation. Methods NOD2 liver-specific knockout mice were used, and diethylnitrosamine (DEN) was used to construct an acute liver injury model. NOD2 knockout mice injected with DEN were used as the Nod2^△hep model group, and injected with DEN B6 / JNju- Nod2^em1Cflox / Gpt (Nod2^{f/ f} ) mice are Nod2^{f/ f} model group, NOD2 knockout mice without DEN injection are Nod2^△hep group, Nod2^{f/ f}mice without DEN injection are Nod2^{f/ f} group. He staining was used to detect the effect of DEN on liver pathological damage, ALT and AST kits were used to detect the changes of serum ALT and AST levels; F4 / 80 immunohistochemical staining was used to detect the number of hepatitis cells and real-time quantitative qPCR was used to detect the gene expression level of inflammatory factors in liver cells; Ki67 immunohistochemical staining and TUNEL staining were used to detect the effects of den on liver cell proliferation and apoptosis Western blot was used to detect the expression of NF-κB, MAPK and STAT3 signaling pathway related proteins Result Compared with Nod2^{f/ f}model group, Nod2^△hep model group mice liver tissue pathological damage was significantly reduced, manifested as cell necrosis and vacuolization, and Nod2^△hepmodel group mice serum ALT and AST levels Significantly decreased (P<0.01). In addition, compared with Nod2^{f/ f} model group, the inflammatory factors TNF-α, IL-6, IFN-γ and IL-1β expression levels、the number of F4 / 80 staining positive cells in liver tissue、the proliferation and apoptosis levels of the hepatocytes in Nod2^△hep model group were significantly reduced ( P<0.01); Western blot expression result showed that the P38, ERK, JNK, p65 and JAK2 / STAT3 protein phosphorylation levels in the liver tissue of the Nod2^△hep model group were significantly lower than those of the Nod2^{f/ f} model group. However, the Nod2^△hep group mice and Nod2^{f/ f}group mice used for control had no obvious abnormalities in the above indicators. Conclusions Loss of NOD2 in the liver can significantly inhibit the inflammation and necrosis of hepatocytes in mice, its mechanism maybe related to the down-regulation of expression of NF-κB, MAPK and STAT3 signaling pathways related factors in liver tissue.