Objective 　To evaluate the effect of the targeted inhibition of myocardial malonyl-CoA decarboxylase (MCD) by ultrasound microbubble mediated MCD-microRNA interference plasmids on cardiac function in rats with myocardial infarction (MI) and its possible mechanism. Methods 　The MCD expression plasmid and four MCD-microRNA interference plasmids to be screened were co-transfected into HEK293 cells. The levels of MCD mRNA were determined by real-time fluorescence quantitative PCR, and interference sequence with the highest rate of suppression was selected. MI model was reproduced by ligating the left anterior descending coronary artery. The 28 rats with myocardial infarction were randomly assigned into four experimental groups: MI + saline (group 1), MI + plasmid (group 2), MI + ultrasound + plasmid (group 3), MI + ultrasound + microbubble + plasmid (group 4), 7 rats in each group. An alternative group of sham-operated + saline served as control. The mixture of the selected interference plasmids and lipid microbubbles were co-transfected once every four days into rats with MI for 4 weeks mediated by ultrasound. After transfection for 28 days, the changes in left ventricular ejection fraction (LVEF), short axis fractional shortening (FS), left ventricular end-diastolic diameter (LVIDd) were examined by echocardiography, and MCD and lactic acid levels were determined by high-performance liquid chromatography method and enzyme-linked immunosorbent assay respectively. Results 　One MCD-microRNA interference plasmid with the highest inhibition rate, which was 82%, was selected according to the result of real-time fluorescence quantitative PCR. In animal experiments, the levels of LVEF and FS in the group 4 were both higher than those in other MI intervention groups (P < 0.05), but significantly lower than those in the control group (P < 0.05). The lactic acid level was lower in group 4 than in other MI-intervention groups (all P < 0.05), but significantly higher than that in the control group (P < 0.05). There was no significant difference in LVIDd level between the intervention groups (P > 0.05), but it was significantly lower than that in the control group (P < 0.05). Conclusion 　That MCD-microRNA interference plasmids were targetedly transfected into infarcted myocardium as mediated by ultrasound microbubble, and they are able to increase malonyl CoA level, reduce lactic acid content, and delay the deterioration of cardiac function, although it has no effect to prevent ventricular dilatation.