The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a key role in immune regulation and has been shown to be dysregulated in inflammatory disease. Cholestatic liver disease due to bile duct ligation is associated with liver inflammation, disrupted bile flow, neuroinflammation, and the development of sickness behavior. Whether AhR activation in a murine model of cholestatic liver disease will attenuate inflammation and prevent the development of sickness behaviors has not been examined. This thesis tested the hypothesis that activation of the AhR will reduce neuroinflammation and sickness behavior in a murine model of cholestatic liver disease. The expression of AhR-controlled genes was examined using quantitative polymerase chain reaction in the liver, pre-frontal cortex, hippocampus, and hypothalamus of sham and bile duct ligated (BDL) mice treated with vehicle or the synthetic AhR agonist beta-naphthoflavone (BNF). Two endogenous AhR ligands indoxyl sulfate (I3S) and indole-3-carbinol (I3C) were also used. We found that the AhR was not activated by I3C and I3S, however BNF upregulated the expression of AhR-regulated genes in the liver and the brain. Acute administration of BNF to BDL mice was able to attenuate the levels of pro-inflammatory cytokines in the liver and the brain, however, BNF was not able to ameliorate the underlying liver injury or sickness behavior development. The immunoreactivity of glial fibrillary acidic protein (astrocyte marker) and ionized calcium binding adaptor molecule 1 (microglia marker) increased in the CA1 region of the hippocampus of BDL mice. Using flow cytometry, we isolated astrocytes and microglia from the hippocampus and found that the proportion of microglia in the hippocampus of BDL mice increased compared to sham mice. However, the proportion of astrocytes in the hippocampus decreased in BDL mice compared to sham mice, with BNF administration causing a further decrease. Overall, this study showed that systemic BNF administration can activate the AhR both in the periphery and the brain and can attenuate inflammation, but not prevent the development of sickness behavior in this model of cholestatic liver disease.