Abstract: OBJECTIVE To investigate the protective effects of tetramethylpyrazine(TMP) on myocardial hypertrophy induced by pressure overload in rats in vivo. METHODS Myocardial hypertrophy model of the rats induced by pressure overload was prepared by constricting abdominal aorta. The operated rats were randomly divided into abdominal aorta constricted model group, three dosage of TMP groups (25, 50, 100 mg·kg^-1) and L-arginine group. The abdominal aorta was not constricted in sham operated control group. The drugs were administered on the next day of operation, and continued for 3 weeks, the cardiac function was assessed. The ratios of left ventricular weight to body weight (LVHI=LVW/BW), left ventricular weight to right ventricular weight (LVW/RVW) and the cardio-myocyte diameters (MD) after dyeing by hematoxylin-eosin were measured. The expressions of aterial natriuretic peptide (ANF, a marker of myocardial hypertrophy) and calcineurin (CaN) mRNA was detected at the transcript levels by real time-PCR. RESULTS Compared with abdominal aorta constricted model group, TMP significantly reduced LVHI, LVW /RVW, MD and left ventricular end-diastolic pressure (LVEDP), but increased ±dp/dtmax, the expressions of ANF and CaN mRNA were significantly suppressed by TMP. CONCLUSION TMP has protective effects on the left ventricular hypertrophy induced by overload pressure in rats, which may be, in partly, mediated by its inhibitory effect on CaN signaling pathway.