Stem cell therapy has been proved to be an effective approach to ameliorate the heart remodeling post myocardial infarction (MI).However, poor cell engraftment and survival in ischemic myocardium limits the successful use of cellular therapy for treating MI.Here, we sought to transplant adipose derivedmesenchymal stem cells (AD-MSCs) with a hydrogel (NapFF-NO), naphthalene covalently conjugated a short peptide, FFGGG, and β-galactose caged nitric oxide (NO) donor, which can release NO molecule in response to β-galactosidase.AD-MSCs, either from transgenic mice that constitutively express firefly luciferase (Fluc), or from VEGFR2-luc mice that express Fluc under the control of VEGFR2 promoter, were co-transplanted with NapFF-NO hydrogel into murine MI models.Bioluminescence imaging (BLI) showed that donor cell surviving was increased in the presence of NapFF-NO hydrogel.Moreover, increasing VEGFR2-luc expression was also tracked in real-time in vivo, indicating NapFF-NO hydrogel stimulated VEGF secretion of AD-MSCs.To investigate the therapeutic mechanism of NapFF-NO hydrogel, cell migration assay, paracrine action of AD-MSCs, and histology analysis were carried out.Our results revealed that condition medium from AD-MSCs cultured with NapFF-NO hydrogel could promote endothelial cell migration.Additionally, AD-MSCs showed significant improvement secretion of angiogenic factors, VEGF, SDF-1 α in the presence of NapFF-NO hydrogel.Finally, postmortem analysis confirmed that transplanted AD-MSCs with NapFF-NO hydrogel could ameliorate heart function by promoting angiogenesis and attenuating ventricular remodeling.In conclusion, NapFF-NO hydrogel can obviously improve therapeutic efficacy of AD-MSCs for MI by increasing cell engraftment and angiogenic paracrine action.