Objective:To investigate the effects and mechanisms of lipoxin A4(LXA4)in attenuating hypoxia/reoxygenation injury in human renal tubular epithelial cells(HK-2). Methods:HK-2 cells were exposed to hypoxia followed by reoxygenation with pretreatment of LXA4. Then the cell viability,γ-GT,NAG and LAP levels,SOD activity and MDA level were determined. The expressions of mRNA and protein of PPARγ and HO-1 were measured using real-time polymerase chain reaction (PCR) and Western blot,respectively. The expressions of HO-1 and Nrf2 were detected by using RNA interference technology through interference PPARγ expression. Results:Pretreatment with LXA4 increased the cell viability and SOD activity,and reduced the γ-GT,NAG,LAP and MDA levels. HO-1 inhibition by ZnPP and siRNA of PPARγ abolished the protective role of LXA4 on the cells undergoing hypoxia/reoxygenation injury. Furthermore,the expressions of HO-1,PPARγ and Nrf2 were increased in the cells pretreated with LXA4 significantly,whereas these overexpressions of HO-1 and Nrf2 were partly blocked by treatment with siRNA of PPARγ. Conclusion:This study reveals that LXA4 pretreatment serves a protective role against hypoxia/reoxygenation injury of human renal tubular epithelial cells via over-expression of HO-1 and activation of PPARγ/Nrf2.