Abstract: OBJECTIVE To investigate the effect of eplerenone(EPL) on the expression of Cleaved caspase-3 in cardiomyocytes induced by palmitic acid(PA). METHODS Neonatal rat cardiomyocytes(NRCMs) were treated with PA and EPL for 24 h. The survival rate of cardiomyocytes was measured by MTT assay. The expression of apoptotic protein Cleaved caspase-3 and autophagy related proteins p62 and LC3 were detected by Western blotting. RESULTS Compared with the normal group, the survival rate of NRCMs was significantly decreased after being stimulated with 200 mmol·L^-1 PA for 24 h(P<0.05), the expression of Cleaved caspase-3, p62 and the ratio of LC3 Ⅱ/Ⅰ in PA group were significantly increased(P<0.05). Compared with the PA group, the survival rate of NRCMs was significantly increased after treated with EPL, the above proteins expression were reduced(P<0.05).CONCLUSION Eplerenone can reduce the expression of Cleaved caspase-3 induced by lipotoxicity by affecting autophagy in cardiomyocytes.