Objective To investigate the effects of preconditioning with ω-3 polyunsaturated fatty acid (ω-3 PUFA) on the second liver injury in rats with traumatic brain injury and hemorrhagic shock (TBIS) and explore the underlying mechanism.Methods Total of 36 male Wistar rats were assigned randomly (random number) into 3 groups (n =12 in each):sham operation group (C),TBIS model group and PUFA pretreatment group.The arterial blood samples were taken for determination of serum levels of ALT,AST and TNF-α.The liver were removed for determination of levels of superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione (GSH),and microscopic examination.Results Compared with group C,the serum levels of ALT,AST and TNF-α and the liver levels of MDA were significantly higher (P ＜0.01),but the liver levels of SOD and GSH in group TBIS and group PUFA were significantly lower (P ＜0.01).The serum levels of ALT,AST and TNF-α and the liver levels of MDA were significantly lower (P ＜ 0.01 or P ＜ 0.05),but the levels of SOD and GSH in liver tissues were significantly higher (P ＜ 0.01or P ＜ 0.05) in group PUFA than those in group TBIS.Histological examination revealed the injury of liver in TBIS group,and the rats in PUFA treated group showed alleviated severity of liver injury.Conclusions The supplementation of ω-3 PUFA can ameliorate acute liver injury in rats with TBIS,which may contribute to inhibition of oxygen free radicals and inflammatory cytokines expression.