The aim of this study was to assess how the administration of prostaglandin E1 incorporated in lipid microspheres (Lipo PGE1) affects liver injury and regeneration after massive hepatectomy in rats. Two hundred and eight male Wistar rats underwent 90% partial hepatectomy. Lipo PGE1 of 1, 10 or 30 μg/kg were administered intraperitoneally at 6 h prior to and 0 and 6 h after hepatectomy. Postoperative increases in serum GOT, total bilirubin, IL-6 and plasma endotoxin levels were significantly suppressed by Lipo PGE1. The depressed phagocytic index and arterial ketone body ratio and hepatic DNA synthesis after 90% partial hepatectomy were significantly enhanced by Lipo PGE1, which resulted in the improvement of survival. Lipo PGE1 might bring about a protective effect on liver injury and an enhancement of liver regeneration after massive hepatectomy.