AIM: To investigate the protective effect and mechanism of alanyl-glutamine dipeptide (Ala-Gln) against hepatic ischemia-reperfusion injury in rats.METHODS: Rats were divided into group C as normal control Group (n=16) and group G as alanyl-glutamine pretreatment (n=16). Rats were intravenously infused with 0.9% saline solution in group C and Ala-Gln -enriched (2% glutamine) 0.9% saline solution in group G via central venous catheter for three days. Then all rats underwent hepatic warm ischemia for 30 min followed by different periods of reperfusion. Changes in biochemical parameters, the content of glutathione (GSH) and the activity of superoxide dismutase (SOD) in liver tissue, Bcl-2and Bax protein expression and morphological changes of liver tissue were compared between both groups.RESULTS: One hour after reperfusion, the levels of liver enzymes in group G were significantly lower than those in group C (P＜0.05). Twenty-four hours after reperfusion, the levels of liver enzymes in both groups were markedly recovered and the levels of liver enzyme in group G were also significantly lower than those in group C (P＜0.01). One and 24 h after reperfusion, GSH content in group G was significantly higher than that in group C (P ＜0.05). There was no statistical difference in activities of SOD between the two groups. One and 24 h after reperfusion, the positive expression rate of Bcl-2 protein was higher in group G than in group C (P＜0.05)and the positive expression rate of Bax protein was lower in group G than in group C (P＜0.05). Histological and ultrastructural changes of liver tissue were inhibited in group C compared to group G.CONCLUSION: Our results suggest that Ala-Gln pretreatment provides the rat liver with significant tolerance to warm ischemia-reperfusion injury, which may be mediated partially by enhancing GSH content and regulating the expression of Bcl-2 and Bax proteins in the liver tissue.