Abstract: AIM To investigate an innovatively designed gene expression product, rAAV-PR39-ADM, which was mediated by recombinant adeno-associated virus co-expressing antimicrobial peptide (PR39) and adrenomedullin (ADM) in the treatment of myocardial infarction (MI). METHODS Rats were randomly divided into sham group, normal saline group (MI+NS), blank adeno-associated virus vector group (MI+AAV-GFP) and treatment group (MI+rAAV-PR39-ADM). MI model was established by ligation of left coronary artery. On the fourth week after modeling, echocardiography and hemodynamics methods were employed to assess the cardiac functions. Infarct size and collagen volume fraction were calculated by pathological staining, 6His-Tag which indirectly represented the expression of PR39 and ADM was tested by immunochemistry, and 6His-Tag and VEGF expressions were measured by Western blot. RESULTS It was found that the cardiac functions were significantly improved and the infarct size was significantly decreased in treatment group. 6His-Tag and VEGF in treatment group were significantly higher than those in MI+NS group and MI+AAV-GFP group (P<0.05). CONCLUSION rAAV-PR39-ADM significantly improves the cardiac functions after myocardial infarction, attenuates the infarct size and promotes angiogenesis.