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Background : Ischemia reperfusion injury of the liver is a common event following hepatic surgery and liver transplantation, but the precise mechanisms are not fully elucidated. Serotonin is known to induce platelet aggregation and vasoconstriction, and plays an important role in thrombus formation. The purpose of this study is to investigate the influence of serotonin on the hepatic microcirculation disturbance after hepatic ischemia and reperfusion (HIR) injury and to evaluate the effect of the administration of the selective S2-serotonergic receptor antagonist (5HTra) under these conditions. Materials and Methods: Adult female rats were divided into two treatment groups: group 1 was assigned as a control and group 2 received S2-serotonergic receptor antagonist (5 HTra) administration. Animals received intraperitoneally either saline (control group) or a selective 5 HTra prior to surgery. As a method for inducing liver ischemia without causing systemic hypotension, we used a partial liver ischemia model, which was performed by clamping the pedicles of the medial lobe. 5 HTra was administered with a dosage of 10 mg/kg intraperitoneally at 15 min before ischemia and 15 min before reperfusion. To estimate the damage of hepatic cells, the levels of aspartate transaminase, alanine transaminase, and lactate dehydrogenase in the serum were measured. Results: The intra-abdominal administration of selective S2-serotonergic receptor antagonist (10 mg/kg) 15 minutes before ischemia and 15 minutes before reperfusion resulted in a significant inhibition of the post reperfusion release of the liver enzymes. Serotonin was detected in the sinusoid of the liver subjected to 90 minutes of ischemia followed by 60 minutes of reperfusion. Conclusion : We conclude that serotonin is strongly involved in the pathogenesis of ischemia reperfusion injury.