The present study was designed to evaluate possible protective effects of purified histaminase from Lathyrus sativus L. seedling on the myocardial injuries upon isoprenaline-induced myocardial infarction in rats. In this regard, blood histamine concentration, creatine kinase-MB (CK-MB) activity, antioxidant status, and histopathological changes of the hearts were measured. A total of 40 adult male Sprague-Dawley rats were divided into five equal groups and treated in the following order: control (normal saline), isoprenaline (isoproterenol 110 mg/kg BW), Isopren.-H1 (isoprenaline plus histaminase 80 U/kg BW), Isopren.-H2 (isoprenaline plus histaminase 120 U/kg BW), and Isopren.-H3 (isoprenaline plus histaminase 160 U/kg BW). Myocardial infarction was manifested by a significant elevation in the level of CK-MB and histopathological findings in isoprenaline group when compared to controls. In contrast, histaminase pretreatment at dose of 160 U/kg prevented isoprenaline-induced histamine release and significantly decreased CK-MB activity as well as histopathological changes in Isopren.-H3 group. A significant increase in the catalase (CAT) and superoxide dismutase (SOD) activities was also observed by histaminase treatment in Isopren.-H2 and Isopren.-H3 groups. Although the activity of glutathione peroxidase (GPx) increased significantly to suppress oxidative stress in isoprenaline group, it was not able to prevent lipid peroxidation (as shown by TBARS concentration) in the heart of rats. In conclusion, the plant-originated histaminase presented as a promising enzyme with antioxidant properties against histamine release and myocardial infarction in rats, and it seems be a suitable therapeutic agent for future clinical trials in humans.