In the present study, we investigated the effect of lipoxin A4 on myocardial ischemia-reperfusion injury (IRI) following cardiac arrest (CA) in a rabbit model. Lipoxin A4 is a metabolite of arachidonic acid in the eicosanoid, it is called "brake signal" for its anti-inflammatory activity. Some inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10), NF-κB p65, infarct ratios, apoptotic index, cardiac troponin I (cTnI), hemodynamic and myocardial structures were measured or observed in different groups. Lipoxin A4 inhibits the expression of IL-1β, IL-6, and TNF-α, the values of the infarct ratios, apoptotic index, the level of serum cTnI and NF-κB p65. Meanwhile, it improves the expression of IL-10, hemodynamic, myocardial structure, and function. These indicate that lipoxin A4 mitigates postresuscitation myocardial IRI in which anti-inflammation and suppression of NF-κB activation may play an important role.