Interruption of hepatic inflow is commonly used to reduce blood loss during extensive liver resection, but may cause liver dysfunction. The present study investigated the effects of platelet-activating factor (PAF) antagonist E5880 on total liver warm ischemia and 70% hepatectomy.Rabbits were used in this study and were divided into four groups: group 1, those treated with only 70% hepatectomy; group 2, those treated with only 20 min Pringle's maneuver; group 3, those treated with both Pringle's maneuver and 70% hepatectomy without pretreatment; and group 4, those pretreated with PAF antagonist E5880 (0.3 mg/kg) followed by Pringle's maneuver and 70% hepatectomy. The remnant liver function was then evaluated after reperfusion.Seven-day survival rates in both groups 1 and 2 were 100%. E5880 treatment significantly increased 7-day survival rate (group 4: 38% vs group 3: 0%, P < 0.05) after a combination of Pringle's maneuver and 70% hepatectomy. The elevations of serum liver enzymes (GOT, GPT, mGOT, and LDH) were significantly inhibited in group 4 at 1 and 4 h after reperfusion. Portal venous pressure and the energy charge of liver were also significantly improved in group 4, compared with those in group 3. Endothelin-1 levels of arterial and portal venous blood progressively increased after reperfusion; however, there were no significant differences between the two groups. Leukocyte infiltration into the liver was significantly inhibited in group 4.E5880 pretreatment has protective effects on liver function after 70% hepatectomy with Pringle's maneuver in rabbits.