Introduction: Chronic liver failure induces hyperammonemia that finally leads to hepatic encephalopathy (HE). It has been shown that HE is associated with alterations in cerebral and cognitive functions. According to previous researches, mitogen-activated protein (MAP) kinases are affected at transcriptional and post-transcriptional levels in HE in response to inflammation induced by hyperammonemia. The aim of the present study was to investigate expression of JNK3 MAP kinase in the hippocampus of rats with hepatic encephalopathy. Methods: Male Wistar rats weighing 300-350 g were used. Chronic liver failure was induced in a group of rats as a model of HE using a common bile duct ligation (BDL). Sham control operation consisted of laparotomy and bile duct identification without ligation and resection. On day 28 after the surgery, the animals were decapitated, their brain were removed from the skull and the hippocampi were dissected bilaterally from both hemispheres of each rat on an ice chilled surface. A real-time PCR and western blotting methods were used for evaluating gene and protein expressions of the JNK3 MAP kinase in the hippocampus. The results were analyzed with independent sample t-test and p<0.05 was defined as statistical significant level. Results: The result of gene expression with real-time PCR revealed a significant increase at mRNA level of JNK3 MAP kinase in the hippocampus in a group of rats as a model of HE compared to the sham control group. The result of western blotting method for protein expression of JNK3 MAP kinase in the hippocampus also showed a significant increase in the group with HE compared to sham control group. Conclusion: It can be concluded that brain inflammation and cognitive impairment in the animals with HE are associated, at least partly, with changes in activation of JNK3 MAP kinase in the hippocampus.