<p><span style="font-size:11pt">Background: To evaluate the efficiency of Menstrual blood Stromal/Stem Cells (MenSCs) administration in Myocardial Infarction (MI), the effects of MenSCs and their derived conditioned Medium (CM) on cardiac function in MI rat model was assessed. </span></p> <p><span style="font-size:11pt">Methods: Animals were divided into four groups including sham group, MI group, MenSCs derived CM group (CM group), and MenSCs suspended in CM (MenSCs+ CM) group. The injection of different groups was carried out 30 min after ligation of left anterior descending coronary artery into the infarct border zone. </span></p> <p><span style="font-size:11pt">Results: The results showed a significant reduction in scar size after injection of MenSCs+CM compared to MI group. Ejection fraction and fractional shortening of MenSCs+CM group were higher than CM and MI group at day 28. Administration of MenSCs+CM led to much more survival of cardiomyocytes, and prevention of metaplastic development. Moreover, human mitochondrial transfer from MenSCs to cardiomyocytes was seen in group treated by MenSCs+CM. Indeed, MenSCs+CM treatment evoked nuclear factor-&kappa;B (NF-&kappa;B) down-regulation more than other treatments. </span></p> <p><span style="font-size:11pt">Conclusion: MenSCs+CM treatment could significantly ameliorate cardiac function by different mechanisms including inhibition of cartilaginous metaplasia, inhibition of NF-&kappa;B and mitochondrial transfer.</span></p>