Introduction: Liver failure is the fourth leading cause of death in the world. Chronic liver failure resulting in a condition known as hepatic encephalopathy. In this disease, neurotransmitter systems are affected leading to cognitive and motor disorders. Mitogen-activated protein kinases (MAPKs) are target molecules in the signaling pathways of inflammatory and neurotransmitter receptors. It has been reported that MAPKs are affected at transcriptional and post-transcriptional levels in hepatic encephalopathy in response to inflammation induced by hyperammonemia. Therefore, the aim of the present study was to investigate gene expression of the main members of MAPK cascades including p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase 3 (JNK3) in the prefrontal cortex of rats with hepatic encephalopathy. Methods: Male Wistar rats weighing 300-350 g were used. A common bile duct was ligated and resected to induce hepatic encephalopathy in one group of rats but sham control operation consisted of laparotomy and bile duct identification without ligation and resection. On day 28 after the surgery, two groups of sham and model of hepatic encephalopathy were decapitated and their brain were removed, fixed in formalin (10%). After 72 h, brain sections at prefrontal area were prepared and stained with Hematoxylin and Eosin. The brains of two other groups from both experimental groups were also removed from the skull and the prefrontal cortex were bilaterally dissected. A RT-PCR method was used for evaluating gene expression of main members of MAPKs including the p38, ERK1/2 and JNK3 in the prefrontal cortex. An independent sample t-test was used to analyze the results of gene expression between the sham control group and the model group with hepatic encephalopathy. Statistical significant level was defined as P<0.05. Results: The results of histopathology at prefrontal area showed inflammatory signs including brain edema and gliosis in r
