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Recent studies have revealed that macrophages suppress inflammatory reactions by producing lipid mediators, called specialized proresolving mediators (SPMs); however, the biological significance of SPMs in tissue repair remains to be fully elucidated in the heart. In this study, we focused on maresin-1 (MaR1) and examined the reparative effects of MaR1 in cardiomyocytes. The treatment with MaR1 increased cell size in cultured neonatal rat cardiomyocytes. Since the expression of fetal cardiac genes was unchanged by MaR1, physiological hypertrophy was induced by MaR1. SR3335, an inhibitor of retinoic acid-related orphan receptor \u03b1 (ROR\u03b1), mitigated MaR1-induced cardiomyocyte hypertrophy, consistent with the recent report that ROR\u03b1 is one of MaR1 receptors. Importantly, in response to MaR1, cardiomyocytes produced IGF-1 via ROR\u03b1. Moreover, MaR1 activated phosphoinositide 3-kinase (PI3K)\/Akt signaling pathway and wortmannin, a PI3K inhibitor, or triciribine, an Akt inhibitor, abrogated MaR1-induced cardiomyocyte hypertrophy. Finally, the blockade of IGF-1 receptor by NVP-AEW541 inhibited MaR-1-induced cardiomyocyte hypertrophy as well as the activation of PI3K\/Akt pathway. These data indicate that MaR1 induces cardiomyocyte hypertrophy through ROR\u03b1\/IGF-1\/PI3K\/Akt pathway. 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