To clarify the pathophysiology of acute liver injury after extended hepatectomy, we investigated the relationship between the site and levels of expression of platelet activating factor (PAF) receptor mRNA, and the blood levels of endotoxin, cytokines, and prostaglandin E2 (PGE2), using a rat model of 70% hepatectomy. After hepatectomy, a significant rise in serum tumor necrosis factor-alpha (TNF-alpha) was observed at 1 hr, the interleukin-6 (IL-6) levels had increased at 3 hr, and PGE2 levels had increased at 6 hr, but there were no significant increases in endotoxin levels in portal vein blood. Overexpression of PAF receptor mRNA in liver tissue was observed as early as 1 hr after hepatectomy, with peak expression occurring at 6 hr, and PAF receptor mRNA was significantly overexpressed in Kupffer cells. The PAF produced in the vicinity of Kupffer cells appears to play a very important role as one of the initial mediators of the acute liver injury that occurs after major hepatectomy.