Objective To investigate the protective effect of quercetin pretreatment on hepatic ischemia- reperfusion injury by autophagy mediated via the AMPK/ mTOR signaling pathway. Methods Rats were randomly divided into control, model, quercetin, chloroquine (autophagy inhibitor) and quercetin+chloroquine groups. Three days before the operation, the quercetin group was administered 0. 1 g / kg quercetin, the chloroquine group was intraperitoneally injected with 0. 02 g / kg chloroquine, the quercetin+chloroquine group was administered quercetin by gavage and chloroquine was injected intraperitoneally at 3 days, and the control and model groups were administered an equal volume of solvent once a day. The rat model of hepatic ischemia-reperfusion was established and rats were sacrificed at 6 hours after reperfusion. Liver function indexes, which included glutamic pyruvate transaminase (ALT) and aspartate acyltransferase (AST), were measured by an automatic biochemical analyzer. Pathological changes of liver tissue were observed by hematoxylin eosin (HE) staining. The serum levels of inflammatory factors, which included interleukin ( IL-6), tumor necrosis factor-α (TNF-α) and IL-1β were measured by enzyme-linked immunosorbent assays. The autophagy rate was calculated by monosulfonamide (MDC) staining. Expression of Beclin1 protein and the phosphorylation of AMPK and mTOR proteins in liver tissue were detected by Western blot. Results In the control group, the liver tissue structure was complete, hepatocytes were arranged in order, and there was no significant necrosis. Compared with the control group, the liver tissue structure of the model group was disordered, the arrangement of hepatocytes was loose, and necrosis had appeared, the levels of ALT and AST, contents of IL-6, TNF-α and IL-1β, phosphorylation level of mTOR protein were significantly higher (P<0.05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly lower (P<0.05). Compared with the model group, the above pathological damage of liver tissue in the quercetin group was alleviated significantly, the levels of ALT and AST, the contents of IL-6, TNF-α, IL-1β and the phosphorylation level of mTOR protein were significantly lower (P< 0. 05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly higher (P<0.05). In the chloroquine group, the above pathological damage of liver tissue was aggravated significantly, the levels of ALT and AST, contents of IL-6, TNF-α and IL-1β and phosphorylation level of mTOR protein were significantly higher (P<0. 05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly lower ( P< 0.05). Compared with the quercetin group, the pathological damage of liver tissue in the quercetin + chloroquine group was more serious, the levels of ALT and AST, contents of IL-6, TNF-α and IL-1β. and phosphorylation level of mTOR protein were significantly higher (P<0.05) and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly lower (P<0. 05). Compared with the chloroquine group, the pathological damage of liver tissue in the quercetin+chloroquine group was significantly reduced, the levels of ALT and AST, the contents of IL-6, TNF- α and IL-1β, and phosphorylation level of mTOR protein were significantly lower (P< 0.05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly higher ( P< 0.05). Conclusions Quercetin pretreatment may activate autophagy mediated by the AMPK/ mTOR signaling pathway in liver tissue of rats with hepatic ischemia-reperfusion injury, thereby reducing the inflammatory response and alleviating liver injury.