Objective. To investigate the protective effects of L‐malate against myocardial ischemia/reperfusion (I/R) injury in rats. Methods. Male Sprague‐Dawley rats were randomly assigned to the following groups: sham (sham), an ischemia/reperfusion (I/R) model group (model), an DMF pretreated group (DMF), and 5 L‐malate pretreated groups (15, 60, 120, 240, or 480 mg/kg, gavage) before inducing myocardial ischemia. Plasma LDH, cTn‐I, TNF‐α, hs‐CRP, SOD, and GSH‐PX were measured 3 h later I/R. Areas of myocardial infarction were measured; hemodynamic parameters during I/R were recorded. Hearts were harvested and Western blot was used to quantify Nrf2, Keap1, HO‐1, and NQO‐1 expression in the myocardium. Results. L‐malate significantly reduced LDH and cTn‐I release, reduced myocardial infarct size, inhibited expression of inflammatory cytokines, and partially preserved heart function, as well as increasing antioxidant activity after myocardial I/R injury. Western blot confirmed that L‐malate reduced Kelch‐like ECH‐associated protein 1 in ischemic myocardial tissue, upregulated expression of Nrf2 and Nrf2 nuclear translocation, and increased expression of heme oxygenase‐1 and NAD(P)H:quinone oxidoreductase 1, which are major targets of Nrf2. Conclusions. L‐malate may protect against myocardial I/R injury in rats and this may be associated with activation of the Nrf2/Keap1 antioxidant pathway.