Objective To investigate the effect of the overexpressed NKx2.5 genes in bone marrow mesen⁃ chymal stem cells（BMSCs）on cardiac function after myocardial infarction by enhancing the SDF⁃1/CXCR4 axis to promote BMSC homing. Methods Lentivirus was used to overexpress NKx2.5 in BMSCs（BMSCNKx2.5 ）. The empty body group，BMSC group，and mouse cardiomyocyte group were used as the control groups. The expressions of SDF⁃1，CXCR4 and NKx2.5 in each group were detected by RT⁃PCR，and the expression of transcription factors NKx2.5，SDF⁃1 and CXCR4 proteins was detected by western⁃blot. BMSCNKx2.5 ，BMSC，and BMSCempty body were injected into the mouse myocardial infarction model through the tail vein. The BMSCNKx2.5 +AMD3100 group was set up. The untreated myocardial infarction group，sham operation group，and normal mouse group were used as the control groups. Changes in the cardiac function of mice with myocardial infarction were detected via Color Dop⁃ pler ultrasound. The expression of NKx2.5，SDF ⁃ 1 and CXCR4 proteins was detected by western ⁃ blot. Results NKx2.5，SDF ⁃1 and CXCR4 in the BMSCNKx2.5 group had the highest expression（P < 0.05）. In vivo experiments confirmed that the BMSCNKx2.5 group exhibited the most significant improvement in cardiac function after myocardial infarction（P < 0.05）. The expression of transcription factors NKx2.5，SDF⁃1 and CXCR4 in BMSCNKx2.5 group was the highest（P < 0.05）. However，when the SDF⁃1⁃CXCR4 axis inhibitor AMD3100 was added，the improvement in cardiac function was insignificant. Conclusion BMSCNKx2.5 can improve myocardial function after myocardial infarction by enhancing the SDF⁃1/CXCR4 axis to promote BMSC homing.