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Introduction To investigate the cardioprotective effect of Micro RNA-21 (miR-21) in murine myocardial infarction ( MI). Methods Forty C57 BL/6 male mice were divided into sham group, MI group, LV- GFP group, and miR-21 group. Mice in the MI group, LV- GFP group, and miR-21 group were subjected to MI by left anterior descending artery ( LAD) ligation, while chest was opened/closed without ligation in sham group. In MI group, expression of miR-21 in the MI area and its surrounding areas was detected at 1st, 2nd, and 4th week after experiment. Subsequently, lentivirus expressing miR-21 and lentivirus that did not express miR-21 were transfected into mice left ventricular cavity of miR-21 group and LV- GFP group, respectively. Cardiac function, MI size, miR-21 expression, collagen I level, fibronectin content, number of α- SMA-positive cells, number of apoptotic cells, apoptosis-related factors were compared between the three groups. Results Compared with sham group, miR-21 levels in MI group were significantly decreased in the 1st week and 2nd week, but were almost the same in the 4th week. Left ventricular fractional shortening ( LVFS) and left ventricular ejection fraction ( LVEF) in the miR-21 group improved compared to the LV- GFP group. In miR-21 group, myocardial infarct size reduced by 36.9% in comparison with LV- GFP group. Compared to sham group, miR-21 expression in the miR-21 group and LV- GFP group decreased significantly. In the miR-21 group, collagen I level, fibronectin content and number of α- SMA-positive cells of miR-21 decreased significantly compared to the LV- GFP group. The number of apoptotic cells in the MI areas of the miR-21 group was significantly less than the LV- GFP group. Compared with the LV- GFP group, Bcl-2 level and the ratio of Bcl-2 to Bax were significantly increased, and the levels of Bax and Caspase-3 decreased. Conclusions Our results suggest miR-21 is an important regulatory molecule in the pathophysiology of MI. [ABSTRACT FROM AUTHOR]