Objective To investigate the difference in tissue distribution of ligustrazine hydrochloride and Salvia miltiorrhiza (Danshen) in Acute myocardial ischemia (AMI) rats. Methods AMI model was induced by subcutaneous injection of isoproterenol hydrochloride. UPLC-MS/MS method was used to determine the content differences of ligustrazine and danshensu in heart, liver, spleen, lung, kidney and brain tissues after single intravenous injection of Danshen injection (DGI), Ligustrazine injection (CGI) and Shenxiong glucose injection (SGI) at different time points. Results After intravenous injection, ligustrazine and danshensu were widely distributed in tissues of AMI rats and reached their peak rapidly. Before and after compatibility, the content of ligustrazine was the highest in brain tissue and the lowest in liver tissue. The content of danshensu in kidney tissue was the highest, and in brain tissue was the lowest, indicating that ligustrazine could penetrate the blood-brain barrier more easily than danshensu, and the main accumulation tissues were different. The AUC of ligustrazine and danshensu in the heart of the target organ was significantly increased (P < 0.001). Conclusion It is speculated that the combination of ligustrazine and salvia miltiorrhiza may enhance the therapeutic effect by increasing the distribution of main pharmacodynamic components in the heart, so that SGI can play a better role.