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Objective: To investigate the regulation of the epidermal growth factor receptor (EGFR) pathway by visfatin and its effect on cardiac hypertrophy. Methods: 60 Wistar male rats were randomly divided into control group, visfatin group and visfatin +AG1478 group, with 20 rats in each group.The cardiac mass index, left ventricular mass index and cardiomyocyte volume of rats in each group were calculated.The total protein content of each group of cardiomyocytes was detected by coomassie bright blue staining, and the protein expression was detected by Western blotting. Results: Compared with the control group, the cardiac mass index, left ventricular mass index, cardiomyocyte volume, protein content, and relative expressions of ANP and BNP were significantly increased in the visfatin group (P<0.05). The relative expression levels of EGFR, p-AKT, p-ERK1/2, p-STAT3, ANP and BNP in cardiac myocytes in the visfatin group were significantly higher than those in the control group and the visfatin+AG1478 group (P<0.05). Conclusion: Visfatin induces hypertrophy in cardiomyocytes by activating the EGFR signaling pathway.