Clinically, myocardial fibrosis is increasingly being recognized as a new therapeutic target for ischaemic heart diseases. The aim of this study was to investigate whether noninvasive multimodal molecular imaging could be used to dynamically assess whether the combination of bone marrow mesenchymal stem cells (BMSCs) and hepatocyte growth factor (HGF) therapy can synergistically attenuate myocardial fibrosis after myocardial infarction (MI). MI was induced in 28 rats by coronary ligation with subsequent injection of BMSCs/HGF, BMSCs, HGF, or saline into the border zone under echocardiography guidance. The therapeutic procedure and treatment effects were tracked and assessed using bioluminescence imaging (BLI) and cardiac magnetic resonance (MR) imaging. Four weeks after transplantation therapy, cardiac MR imaging demonstrated that BMSC/HGF-treated animals showed better ejection fractions (p < 0.001) and smaller scar sizes (p < 0.001) than those treated with BMSCs or HGF alone. Histopathological and immunohistochemical results showed less collagen deposition, increased microvessel densities and more regenerative cardiomyocytes in the BMSC/HGF-treated animals than in those receiving HGF or BMSCs alone (all p < 0.05). Multimodal molecular imaging allows a specific and timely strategy to be established for dynamically tracking treatment and noninvasively assessing the therapeutic effects. Under echocardiography guidance, intramyocardial injection of transfected HGF with BMSCs can enhance cell survival, improve cardiac function, stimulate angiogenesis, and reduce myocardial fibrosis in a post-MI rat model.