We investigate changes in gene expression of GluN1 subunit of N-Methyl-D-Aspartate (NMDA) receptor in the prefrontal cortex (PFC), hippocampus and striatum in a rat model of hepatic encephalopathy (HE). We used male Wistar rats in which HE was induced after a common bile duct ligation (BDL). The animals were divided into three sets, and each set included three groups of control, sham operated and BDL. In the first set of animals, blood samples collected for biochemical analysis on day 21 of BDL. In the second set, changes in nociception threshold was assessed on day 21 of BDL using a hotplate test. In the third set, whole brain extracted, and the PFC, the hippocampus and the striatum in each rat were immediately dissected. We used a semi-quantitative RT-PCR method for evaluating the GluN1 gene expression. The biochemical analyses showed that plasma levels of ammonia and bilirubin in BDL rats were significantly increased compared to the sham control group on day 21 of BDL (P < 0.01). Nociception threshold was also increased in rats with BDL compared to sham group (P < 0.001). The results revealed that the GluN1 gene expression at mRNA levels in BDL group was decreased by 19 % in the PFC (P < 0.05) but increased by 82 % in the hippocampus (P < 0.01) compared to the sham control group; however, no significant change was observed in the striatum. It can be concluded that HE affects the GluN1 gene expression in rat brain with a site-specific pattern, and the PFC and hippocampus are more sensitive areas than striatum.