Cobalt-protoporphyrin (CoPP) dependent induction of heme oxygenase (HO)-1 was shown to protect from ischemia-reperfusion injury, which is still a major source of graft loss after liver transplantation. The impact of HO-1 on postoperative liver regeneration, especially in reduced-size grafts has yet not been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial hepatectomy. Male Wistar rats underwent partial (70%) hepatectomy under temporary inflow occlusion (30 min). One group of animals received CoPP (5mg/kgBW) 24 hours prior to surgery to induce HO-1 overexpression at the time of surgery, while the second group served as non-treated controls. At postoperative day 1, 4, 7, and 10 animals were exsanguinated, and blood and liver samples were stored for enzymatic (AST and ALT levels) and histological (mitotic index) analysis (n=5 each day). Additionaly, postoperative body weight and weight of the remnant liver were measured. Although postoperative AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals earlier recovered from surgery as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 vs. 20 per 2.000 hepatocytes) as compared to non-treated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative Cobalt-protoporphyrin (CoPP) administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression might also be beneficial for reduced-size liver grafts without affecting their proliferative capacity.