Objective:To investigate the possible mechanisms of signal transduction pathways of heme oxygenase(HO)-1 expression induced by lipoxin A4 (LXA4) in H9c2 cardiomyocytes. Methods:H9c2 cells were exposed to hypoxia followed by reoxygenation with or without pretreatment of LXA4,nuclear factor-E2 related factor 2 (Nrf2) inhibitor(ATRA),p38MAPK inhibitor(SB203580),LXA4 combined with ATRA,and LXA4 combined with SB203580. The mRNA transcription and protein expression of HO-1,Nrf2 and p38MAPK was examined by RT-PCR,Western blot and immunofluorescence staining. Results:Compared with hypoxia/reoxygenation group,the mRNA transcription and protein expression of HO-1 in H9c2 cardiomyocytes pretreated with LXA4 increased significantly(P < 0.05). The expression of HO-1 in H9c2 cardiomyocytes decreased (P < 0.05) after treated with ATRA or SB203580. ATRA blocked the nuclear accumulation of Nrf2 and decreased HO-1 protein expression induced by LXA4 pretreatment(P < 0.05). SB203580 inhibited the phosphorylation level of p38MAPK and decreased HO-1 protein expression induced by LXA4 pretreatment(P < 0.05). Conclusion:LXA4 can induce HO-1 over-expression which has protective effect on H9c2 cardiomyocytes of hypoxia/reoxygenation injury. Its mechanism is related to p38MAPK/Nrf2 signal transduction pathways.