Objective(s):Hepatic encephalopathy induces cognitive disturbances. Patients show neuroinflammation due to accumulation of toxic substances. Frankincense has neuroprotective and anti-inflammatory properties. Accordingly, we intended to evaluate the impact of frankincense on memory performance, inflammation, and the amount of hippocampal neurons in bile duct-ligated rats.Materials and Methods:The bile duct was ligated in three groups of adult male Wistar rats (BDL groups). In two of these groups, frankincense was administered (100 or 200 mg/kg; by gavage) starting from one week before surgery to 28 days after surgery. The third BDL group received saline. In the sham group, the bile duct was not ligated and the animals received saline. Twenty-eight days after surgery, spatial memory was evaluated by the Morris water maze test. Five rats from each group were sacrificed to measure the expression of the hippocampal tumor necrosis factor-alpha (TNF-α). Three rats from each group were perfused to determine the amount of hippocampal neurons.Results:Bile duct ligation impaired memory acquisition, while frankincense amended it. Bile duct ligation significantly increased the expression of TNF-α. Frankincense reduced TNF-α in BDL rats, significantly. The number of neurons in the hippocampal CA1and CA3areas was significantly lower in the BDL group and in the group that received frankincense (100 mg/kg) equated to the sham group. Frankincense (200 mg/kg) augmented the amount of neurons in the CA1area, slightly and in the CA3area, significantly.Conclusion:The results indicate the anti-inflammatory and neuroprotective effects of frankincense in bile duct ligation-induced hepatic encephalopathy.