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Objective(s): The aims of the present study were to investigate the expression of calcium sensing receptor (CaSR) at different times in acute myocardial infarction (AMI) rat myocardial tissue after mouse embryonic stem cells (mESCs) transplantation treatment and to assess its effects on apoptosis and oxidative stress of cardiomyocytes. Materials and Methods: The AMI rats were treated with mESCs, Calindol (a CaSR agonist) and Calhex231 (a CaSR inhibitor). Serum measurements, Echocardiographic analysis and TUNEL assay were performed. Myocardial ultrastructure changes were viewed by electron microscopy. Additionally, western blotting was used to detect the protein expressions. Results: Compared to the sham group, it was found that the expression levels of CaSR, caspase-3, cytoplasmic cytochrome C (cyt-C) and Bcl2-associated x (Bax), and the levels of Malondialdehyde (MDA) were significantly increased in both AMI and AMI + mESCs + Calindol groups with the development of myocardial infarction. Furthermore, the ultra-microstructure of cardiomyocyte was highly damaged, the expression levels of mitochondrial cyt-C and B-cell lymphoma 2 (Bcl-2) were significantly decreased, and there was decreased activity of superoxide dismutase (SOD). However, the combination of Calhex231 and mESCs transplantation could inhibit these changes. Conclusion: Our results suggested that CaSR expression in myocardial tissue of AMI rats was increased over time, and that Calhex231 could enhance the efficacy of ESCs transplantation for the treatment of AMI, which would be a new therapeutic strategy for the treatment of AMI. [ABSTRACT FROM AUTHOR]