The pathogenesis of hepatic allograft rejection remains unclear. We aimed to clarify the early role of intercellular adhesion molecule-1 (ICAM-1)-mediated cell recruitment in chronic hepatic rejection. Liver transplantation was performed in Lewis to Lewis rats (isograft controls) and Lewis to Brown Norway rats (allograft rejection group). The allografted rats were treated with either ICAM-1 antisense oligonucleotides (10mg/kg/day x 6 days, i.p.) or a control preparation (either ICAM-1 missense oligonucleotide or normal saline). Hepatic leukocyte recruitment in vivo was studied on day 6 using intravital microscopy. Liver histology, biochemistry and survival rates were also examined. Leukocyte adhesion in terminal hepatic venules was significantly increased in the rejection group compared to isograft controls. Antisense ICAM-1 in the allografted group effectively reduced leukocyte adhesion. Histology and liver chemistry were less deranged in the antisense-treated groups compared to control-treated allografted rats. In the allograft groups, survival was significantly prolonged in the antisense-treated rats (42.3±1.2 days) compared to the controls (25.2±2.7 days). These results showed that early leukocyte recruitment in the hepatic microvasculature of rejecting allografts is ICAM-1-dependent, and suggest that impacting on early cell recruitment can significantly ameliorate chronic rejection.