Abstract: AIM To explore the feasibility and effectiveness of treating ischemic heart disease by delivery of bone marrow mesenchymal stem cells (MSCs) using needle-free injection. METHODS Thirty-two dogs were randomly divided into myocardial infarction (MI) group, needle-free injection of normal saline(NS) group, needle injection of mesenchymal stem cells(N+MSCs) group, and needle-free injection of mesenchymal stem cells (N+MSCs) group. Before operation, acute myocardial infarction model was produced by ligation of the left anterior descending coronary artery. No treatment, delivery of normal saline using needle-free injection, delivery of stem cells using needle injection and delivery of stem cells using needle-free injection was completed, respectively. done at the myocardial infarction area in the 4 groups. Hemodynamic monitoring was performed after the 6-week treatment. The hearts were harvested and sectioned for histological and immunohistochemical examination, and the infarct size and the number of small vessels were measured after the animals were sacrificed. RESULTS In group N+MSCs and group NF+MSCs, the infarct area was replaced by fibrous connective tissue and newborn small blood vessels were observed. Compared with other groups, the left ventricular end diastolic pressure (9.00±3.2) mmHg was decreased, the maximum rise rate (841.86±72.85) mmHg/s and the maximum decline rate (-787.29±45.08) mmHg/s of left ventricular pressure were increased, the infarct size (18.59±3.58)% was decreased and the number of newborn small vessels (9.57±2.23) increased in the group with delivery of stem cells using needle-free injection (P<0.05). CONCLUSION It is safe and effective to treat the ischemic heart disease with the needle-free injection of stem cells.