Objective：To discuss the role of 5-hydroxytryptamine3（5-HT3） receptor antagonist in the prevention of pressure overload induced myocardial hypertrophy. Methods：Thirty-two Kunming mice were randomly divided into four groups：sham-operation group（n=8），transverse aortic constriction（TAC） group（n=8），TAC + ondansetron（Ond） group（n=8） and TAC + tropisetron（Tro） group（n=8）. TAC operation was performed and Ond and Tro intervene was followed on 3 d postoperatively. Rats were killed 4 weeks later and their body weight，heart weight，left heart weight，heart/weight ratio and left ventricular/weight ratio were measured and counted. Plasma norepinephrine（NE） levels were detected and heart pathological Masson staining was conducted. Eighteen Kunming mice were randomly divided into control group（n=6），Tro group（n=6） and Ond group（n=6）. TAC operation was not performed and changes in plasma NE levels were observed. Results：Ond and Tro reduced the elevated plasma NE levels in mice with cardiac hypertrophy（F=7.96，P=0.001）. Ond and Tro exerted postive effect on pressure ouerload induced myocardial hypertrophy. Conclusions：5-HT3 receptor antagonists can protect cardiac hypertrophy and restore desensitization of cardiac adrenergic responsiveness，the mechanism of which may be through reducing the sympathetic activity.