Hepatic encephalopathy (HE) is a syndrome that may develop with liver failure. Ammonia and inflammation are central to induce HE and also important therapeutic targets in the management of the disease. Mitogen-activated protein (MAP) kinases are affected in HE in response to inflammation induced by hyperammonemia. Nowadays mesoporous materials have received considerable attention as a drug delivery vehicle for loading drugs as well as large biomolecules. The aim of the present study was to investigate the effects of mesoporous silica SBA-15 functionalized with tryptophan (tryptophan-SBA-15) on Jnk3 MAP-kinase gene expression in the prefrontal cortex (PFC) of the HE model rats. Male Wistar rats weighing 300-350 g were divided into two groups of sham control and HE model group. HE model rats were undergone common bile duct ligation (BDL). A dose of 0.2 mg/kg tryptophan-SBA-15 was injected subcutaneously every 48 hours for 28 days of an experimental period. On day 28 after the surgery, the animals were decapitated, their brain was removed and the PFC of each rat was dissected. Gene expression of Jnk3 was evaluated by a real-time PCR method. The results of gene expression showed that the Jnk3 gene expression was increased in the PFC of HE model group treated with saline. The results also showed that HE model rats treated with tryptophan-SBA-15 decreased the elevation of Jnk3 gene expression. In conclusion, mesoporous tryptophan-SBA-15 treatment could play a role in altering the Jnk3 gene expression in the PFC of HE rats, which may affect brain inflammation.