Background: Acute pancreatitis (AP) has an effect on both inflammatory/autoimmune processes and psychological states, but the pathophysiological causes of pancreatic encephalopathy in the brain are unclear. We hypothesized that the peripheral immune/inflammatory response during AP can affect indolamine 2,3-dioxygenase (IDO) expression and serotonin content in the brain. Methods: About 210 male Sprague Dawley rats were randomly divided into five groups: control (0 h) and 6 h, 24 h, 48 h and 72 h experimental groups. Acute pancreatitis was induced by an injection of a sodium taurocholate solution via a cannulated bile-pancreatic duct. We measured the plasma TNF-alpha and IL-6 levels; serotonin, 5-HIM and the protein concentration levels of IDO and monoamine oxidase A (MAO-A) were evaluated in the striatum, hippocampus and left prefrontal cortex. Results: The IL-6 and the TNF-alpha levels increased in the 24 h, 48 h and 72 h groups. The IDO concentrations of both the 72 h group in the hippocampus and 48 h, 72 h groups in the prefrontal cortex increased; in the corpus striatum, the IDO concentrations fluctuated without statistical significance. The MAO-A protein concentration of the 6 h and 24 h groups decreased in the striatum, hippocampus and prefrontal cortex. There were no statistically significant differences found in the serotonin and 5-HIM concentrations. Conclusions: During the process of AP, cytokines, such as IL-6 and TNF-alpha, may play a role in activation of neuronal pathways utilizing the metabolic enzyme IDO, which may play an important role in determining the mental symptomatology accompanying AP. Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.