Objective: To investigate the effect of tacrolimus (FK506) on myocardial infarction, and to further explore its function mechanism. Material and methods: C57BL/6J mice were randomly divided into three groups: the sham group, the control group and the FK506 group. Anterior descending branch ligation was conducted in the control and the FK506 groups, while sham operation was conducted in the sham group. Mice in the sham and the control groups were intragastrical administration with saline, while the FK506 group were with FK506. Heart function were detected by echocardiogram at 3rd day or 21st day after MI. Hearts were harvested at 3rd day or 21st day after MI for the detection of apoptosis, autophagy, mTOR and NF-kappa B pathway. Results: FK506 treatment increased survival rate and cardiac function in mice after MI. It decreased infarction area, inflammation reaction and apoptosis. To further study the mechanism of FK506 protection effect, we discovered it could increase autophagy via inhibit mTOR pathway. Conclusion: FK506 protect heart function after MI as it improved myocardial cells autophagy process via inhibiting mTOR pathway. (C) 2017 Elsevier Inc. All rights reserved.