Prostaglandins (PGs), metabolites of arachidonic acid, and other lipid mediators produced by phospholipases C (PLC) and D (PLD) are thought to play important roles in hepatocyte proliferation. The present study examined lipid-mediated signaling in the rat liver after partial hepatectomy (PH). Rats were killed 1-48 h after 70% PH and the remaining liver tissue was removed. The mRNA and protein levels of some signaling molecules were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The levels of hepatocyte growth factor (HGF) mRNA showed a biphasic change, peaking 3 h and 9 h after PH. The expression of PLCdelta4 peaked at 12 h, but no significant changes in the expression of PLCbeta1 and PLCgamma1 were seen after PH. T he enzymes involved in PG production, namely, the expression of cytosolic PLA2 and cyclooxygenase 1 (COX1), remained constant after PH. However, the mRNA of COX2 increased transiently at 3 h, and Western blot analysis showed an increase in COX2 protein at 12 h. The expression of PLD1b peaked at 9 h and PLD1a at 12 h, whereas the expression of PLD2 remained consistent for 24 h. These results suggest that transcriptional controls may act for PLCdelta4, PLD1a/b, and COX2 during hepatocyte regeneration after PH.