Abstract Background: Ischaemic Preconditioning is an efficient maneuver to ameliorate liver injury by induction of endogenous defence against ischemia. Propofol is widely used in general anesthesia, and it has been reported to protect various organs against ischemia-reperfusion injury (IRI), including liver. Aim of Study: To study hepatoprotective effects of ischemic preconditioning (IP) and/or propofol, and the possible under-lying mechanisms in rats. Material and Methods: 30 Male Spraguee Dawley rats were divided into 5 groups: Sham group (n 6), non-IP group (n 6; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion), and IP group (n 6; IP applied as 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of ischemia, propofol group (n 6) infused 800µg/ kg/min 45 minutes of hepatic ischemia followed by 2 hours of reperfusion, propofol and IP group n 6. Anesthesia was maintained with intraperitoneal xylazine. Liver enzymes, histopathological changes, and cytokine expression were assessed. Results: The Ischaemic Preconditioning, propofol and Ischaemic Preconditioning-propofol groups showed signifi-cantly lower liver enzyme levels and reduced the histologic scoring of liver 2 hours after reperfusion compared to the non-IP group. Lactate dehydrogenase activity and interleukin-6 mRNA levels were significantly higher in the non-IP group than in the sham and IP groups. Conclusions: Our results demonstrate that IP and propofol significantly attenuated hepatic IRI. The principal mechanism of the protective effects through reduced expression of the IL-6 pro-inflammatory cytokine and propofol antiapoptic effect with subsequent reduction of the degree of necrosis.