The aim of this study was to evaluate the role of the pro-apoptotic molecule Fas Ligand (FasL) in 120 min normothermic ischemia-reperfusion (I-R) induced apoptosis in rat liver treated or not with Z-Asp-cmk caspase inhibitor. Rats were divided into two groups: group 1, control, PBS administration; group 2, Z-Asp-cmk treatment. Z-Asp-cmk was injected intravenously, 2 min before induction of 120 min of normothermic liver ischemia. Immunohistochemical detection of apoptotic liver cells was carried out using the TUNEL method. Fas and FasL expression were measured by qualitative reverse transcription polymerase chain reaction (RT-PCR), Northern and western blot, and by immunofluorescence labeling, in ischemic and non-ischemic liver lobes at different times after reperfusion. FasL mRNA and protein expression were increased in ischemic liver, while Fas receptor mRNA levels remained unchanged. Pre-treatment of rats with Z-Asp-cmk caspase inhibitor reduced liver apoptosis, but did not modify FasL mRNA levels. These results suggest that the pro-apoptotic molecule FasL is involved in the induction of liver apoptosis following I-R.