Objective: To observe the protective effect of pirinixic acid on cold storage injury to rat liver. Methods: Sixty SD rats were equally randomized into pirinixic acid pretreatment group and control group. Rats in pirinixic acid pretreatment group were given pirinixic acid [3 mg/(kg·d)] at 2 d, 1 d and 1 h before surgery by tail vein injection, and rats in control group were given vehicle at the same volume instead. The livers were then removed from rats of the two groups and preserved in 4 oC℃ Ringer’s solution. Liver specimens of the two groups were studied after cold preservation for 0 (before cold preservation), 2, 4, 6 and 8 h respectively, and 6 specimens were obtained in each group at each time point. The mRNA and protein expression levels of peroxisome proliferator-activated receptors α (PPARα) were detected by RT-PCR and Western blot, respectively. The activities of nuclear factor-κB (NF-κB) in hepatic cells were measured by using immunohistochemical staining, and pathological examinations were also performed. Results: With prolongation of the preservation time, the expression levels of mRNA and protein of PPARα in the liver tissues were decreased, and the pathological scores of liver increased gradually in both groups, but in the same time points, the expression levels of mRNA and protein of PPARα in pirinixic acid pretreatment group were higher than those in control group, and the pathological score of pirinixic acid pretreatment group was lower than that of control group, and all the differences had statistical significances (all P<0.05). Except for the control group at 8 h time point, the activities of NF-κB in hepatocytes of the both groups were increased gradually with the extension of the preservation time, and NF-κB activity of pirinixic acid pretreatment group was significantly lower than that of control group at the same time points (all P<0.05). Conclusion: Pirinixic acid has protective effect against cold preservation injury of liver in rats, and its mechanism is probably associated with up-regulating PPARα expression and inhibiting NF-κB activation.