We have previously reported that oxygenated warm perfusion prior to cold preservation (preperfusion) improved the function and viability of liver grafts from non-heart-beating donors (NHBD) using an ex vivo perfusion model. In this study, we evaluated the signaling pathway underlying these effects as well as the additive effect of preperfusion administration of edaravone, a free radical scavenger. Preperfusion treatment suppressed activation of JNK, p38 MAPK, and ERK. The addition of edaravone provided an insignificant increase in bile production and a trend to a decrease in TUNEL-positive cells. Oxygenated perfusion prior to cold preservation improved the function and viability of the grafts from NHBD, which accompanied impairment of MAPK activation. Moreover, the addition of edaravone significantly enhanced the effects of preperfusion.