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Habitual chewing of areca nut increases the risk of cardiovascular disease mortality, but less report demonstrate the toxic mechanism of areca nut on heart. To investigate toxicity of areca nut on cardiomyocytes, we induced the heart injury with arecoline to evaluate the acute damage of areca nut on heart. Different concentrations of are coline (lowdosage: 5 mg/kg/day and high dosage 50 mg/kg/day) were injected into Sprague‐Dawley rat via intra‐peritoneal method for 21 days to create negative effects of arecoline on cardiomyocyte. Themyocardial architecture of the rat heart was observed. The arecoline‐induced apoptotic proteins were analysed via western blotting. The myocardialarchitecture of heart was injured with arecoline and TUNEL stain was also shown are coline‐induced cardiac apoptosis. Arecoline promoted the protein expression of both Fas dependent snd mitochondrial dependent apoptosis. In summary, arecoline induces cardiac toxicity and apoptosis by inducing both death receptor and mitochondria‐dependent apoptotic pathways on heart.