Myocardial infarction (MI) is an irreversible event caused by cardiac ischemia and may be fatal. Studies reported that increased intake of n-3 polyunsaturated fatty acids (PUFA) namely, eicosapentaenoic acid and docosahexaenoic acid reduce the risk of cardiovascular disease and lower the incidence of MI. Nonetheless, the cardioprotective effect of plant n-3-PUFA such as α-linolenic acid (ALA) in the diet is not conclusive. In this study, Sprague Dawley rats were supplemented with isocaloric diets enriched with ALA rich flaxseed (FS) and flaxseed oil (FSO), and normal chow (Control) for 4 weeks. MI was induced by isoproterenol (ISO) injection. Results showed that all ALA-enriched diets displayed cardioprotection against MI. The heart to body weight ratio, plasma LDH activity and plasma cTnI were reduced compared to ISO and was prominent in FS diet. ALA and EPA were up-regulated in both tissues and plasma by ALA-diets compared to Control and remained higher than ISO groups. Notably, LOX-mediated HETEs decreased whereas LOX-mediated HDHAs were elevated in both tissues and plasma of ALA-enriched diets compared to ISO. In addition, non-enzymatic oxidized products from arachidonic acid including 15-F2t-IsoP were reduced in both tissues and plasma of MI rats supplemented with ALA-enriched diets while those from n-3 PUFAs including F4-NeuroPs, PhytoPs and PhytoFs were elevated compared to control. ALA-enriched diets particularly flaxseed reduced gene expressions of inflammatory cytokines namely IL-1β, IL-6 and TNFα and prevented the down regulation of antioxidant catalase in the heart tissues. In conclusion ALA-enriched diets potentially exerted cardioprotection through the regulation of anti-inflammatory and anti-oxidative mediators from n-3 PUFA autooxidation.