Objective: To investigate the protective effect of ambroxol on hepatic ischemia reperfusion injury (I/RI) in rats and its mechanism. Methods: Eighteen male Wistar rats were equally randomized into sham operation group, hepatic I/RI model group (model group) and ambroxol pretreatment+hepatic I/RI model group (ambroxol pretreatment group). Hepatic I/RI model was induced by 30-min hepatic inflow occlusion followed by reperfusion, and rats in ambroxol pretreatment group were injected with ambroxol (100 mg/kg) 20 min prior to ischemia, while those in control group were treated with normal saline of the same volume instead. Rats were sacrificed 6 h after surgery, their serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and liver pathological changes were observed. Meanwhile, the superoxide dismutase (SOD) activity, and glutathione (GSH) and malondiadehyde (MDA) contents as well as the caspase-3 activation in rat liver tissues were also measured. Results: In either model or ambroxol pretreatment group compared with the sham operation group, the serum levels of ALT and AST were significantly increased (both P<0.05); the liver tissues presented evident pathological changes; the liver SOD and GSH contents were significantly decreased while the MDA level was significantly increased (all P<0.05); the caspase-3 activation in liver tissue was significantly increased (both P<0.05). However, the amplitudes of all the above changes were significantly lower than those of model group (all P<0.05). Conclusion: Ambroxol pretreatment can reduce hepatic I/RI in rats, and the mechanism may probably be associated with the augmentation of the anti-oxidant and anti-apoptotic signaling pathway.