Objective:To investigate the role and mechanism of phloroglucinol in hepatic ischemia reperfusion injury. Methods:Forty C57BL/6 mice were randomly divided into four groups on average,named as sham group,IR group,IR+Phlo group,and IR+PBS group. The sham group only separated portal vein without clipping,while partial liver ischemia reperfusion model (70%)was established in other three groups. RAW264.7,a mouse normal macrophage cell line,was incubated with or without phloroglucinol followed by stimulation of LPS in vitro. We evaluated the degree of liver injury by examining the levels of serum ALT and AST and histopathology graded by Suzuki’s score. Expressions of liver IL-1β and TNF-α mRNA were detected in real-time qPCR. ELISA was used to measure the levels of supernatant IL-1β and TNF-α of RAW264.7. The expression of phospho-p65 in RAW264.7 was assessed by western blot. Results:The degree of liver injury and the levels of liver IL-1β and TNF-α mRNA in IR+Phlo group decreased compared to those in IR and IR+PBS groups (P < 0.05). Preincubation with phloroglucinol could significantly inhibit the ablity of secretion of IL-1β and TNF-α by RAW264.7 (P < 0.05),which involved the supression of the activation of NF-κB. Conclusion:Phloroglucinol plays a protective role during hepatic ischemia reperfusion injury,which is partially relates to the supression of the activation of NF-κB in macrophage.