Aim To explore the effect of salvia magnesium lithospermate B (MLB) on myocardial ischemia-reperfusion (IR)-induced cells programmed necrosis and its mechanism. Methods Myocardial infarction model was established by occlusion of the left anterior descending coronary artery in rats. After ischemia 1 h and reperfusion for 3 h, myocardial IR injury model was established. Rats were randomly divided into 7 groups:normal control group, sham operation group, IR group, MLB low dose (10 mg/kg)＋IR group, MLB high dose (30 mg/kg)＋IR group, necrostatin-1 (Nec-1; 3 mg/kg)＋IR group and solvent (normal saline)＋IR group (n＝6~8). Myocardial infarct area was detected by triphenyltetrazolium chloride staining. HE staining was used to observe the morphological changes of myocardial tissue. Serum creatine kinase (CK) activity was measured by spectrophotometry. The expression levels of programmed necrosis associated protein receptor interacting protein kinase 1 (RIPK1) and RIPK3 were detected by Western blot. Results High dose of MLB could significantly reduce the myocardial infarct size and CK release, and improve the myocardial tissue structure of IR rats, with the inhibition of RIPK1 and RIPK3 protein expression, which were better than the positive control drug Nec-1. Conclusion MLB has the function of resisting myocardial cell programmed necrosis, and its mechanism is related to the inhibition of RIPK1 and RIPK3 protein expressions.