Apigenin is a dietary flavonoid that exists copiously in several herbs and vegetables. It exhibits anti-inflammatory, anti-mutagenesis, anti-proliferative and antioxidant properties. The present work aimed to investigate some of mechanisms underlying protective potential of apigenin in hepatic ischemia-reperfusion injury. Rats were divided into four groups; sham-operated, sham-operated pretreated with apigenin (25 mg/kg, p.o.), ischemia/reperfusion (I/R) (30 min ischemia and 1 h reperfusion) and I/R pretreated with apigenin. Compared with I/R group, pretreatment with apigenin markedly reduced transaminases levels and ameliorated tissue histopathological changes. Apigenin significantly reduced high mobility group box 1 (HMGB1) expression and suppressed liver tumor necrosis factor- α (TNF-α), nuclear factor κB (NF-κB) and myeloperoxidase (MPO) activity. Moreover, apigenin restored reduced glutathione (GSH), decreased liver lipid peroxidation, and boosted glutathione peroxidase (GPx) activity in addition to attenuation of apoptosis by increasing Bcl-2/Bax ratio. It may thus be concluded that inhibition of HMGBI by apigenin plays a role towards its antioxidant, anti-inflammatory as well as anti-apoptotic properties which are involved in conferring its hepato-protective properties