Although acupuncture therapy, as a preventive and therapeutic technique, is low or no risk for some cardiovascular diseases, its role in safeguarding myocardial hypertrophy (MH) has not been clarified. Therefore, this study focused on examining whether electroacupuncture (EA) can alleviate MH by up-regulating tryptophan 5-serotonin (5-HT) metabolism, depressive disorder, and gastrointestinal dysfunction in MH rat models. We evaluated the effect of EA on myocardial ischemia in the ISO-induced myocardial hypertrophy (MH) rat model. Forty SpragueDawley (SD) rats aged 3 months were randomly divided into normal group, model group, EA group, and sham EA group with 10 rats in each group. Heart weight/body weight ratio (HW/BW) and left ventricular weight/body weight ratio (LVW/BW) were used to evaluate the regression of MH. Cardiac pathology was evaluated by ultrastructural observation and hematoxylin and eosin (H&E) staining. Sucrose preference test (SPT), forced swimming test (FSW), and open-air test (OFT) were used to study depressive Although acupuncture therapy, as a preventive and therapeutic technique, is low or no risk for some cardiovascular diseases, its role in safeguarding myocardial hypertrophy (MH) has not been clarified. Therefore, this study focused on examining whether electroacupuncture (EA) can alleviate MH by up-regulating tryptophan 5-serotonin (5-HT) metabolism, depressive disorder, and gastrointestinal dysfunction in MH rat models. We evaluated the effect of EA on myocardial ischemia in the ISO-induced myocardial hypertrophy (MH) rat model. Forty Sprague – Dawley (SD) rats aged 3 months were randomly divided into normal group, model group, EA group, and sham EA group with 10 rats in each group. Heart weight/body weight ratio (HW/BW) and left ventricular weight/body weight ratio (LVW/BW) were used to evaluate the regression of MH. Cardiac pathology was evaluated by ultrastructural observation and hematoxylin and eosin (H&E) staining. Sucrose preference test (SPT), forced swimming test (FSW), and open-air test (OFT) were used to study depressive behavior. The gastric retention and intestinal transport were evaluated by carbon powder labeling and the expression of 5-HT in the cerebral cortex and ileum was detected by immunohistochemistry. Depression-like symptoms in rats can be relieved by EA therapy. For instance, the consumption rate of sucrose solution was higher, the total distance and central distance in the open field test were increased, and EA treatment could reduce the immobility time of these rats. Swimming, struggling and immobility latencies were also increased in the forced swimming test. After EA treatment, the expression of 5-HT in the cerebral cortex and ileum increased. Finally, we found that EA ameliorated ischemia, depression, and gastrointestinal dysfunction in ISO-induced MH rats, which may be related to 5-HT metabolism.