Abstract: Objective: To compare the effects of long-term interval training with different intensities on pathological cardiac hypertrophy in spontaneously hypertensive rats (SHR) , and explore the relationship between exercise intensity and health effect.Methods: Forty-five male SHR were randomly divided into a sedentary group (SHR-SED) , a moderate-intensity interval training group (SHR-MIIT) , or a HIIT group (SHR-HIIT) ; another fifteen age-and sex-matched Wistar-Kyoto (WYK) rats were set as a normotensive group. Rats in SHR-MIIT and SHR-HIIT groups were performed 18 weeks of MIIT or HIIT training, respectively, and WYK and SHR-SED groups were keep sedentary during experiment. 48 hours after the last training, the caudal artery pressure was measured by using non-invasive blood pressure tester; the cardiac structure and function were detected by using echocardiogram; the myocardial cross sectional area (CSA) and interstitial collagen volumetric fraction (CVF) were obtained by H&E and Masson staining; RT-PCR was used to measure the mRNA levels of atrial natriuretic peptide (ANP) , brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) ; Western blotting was used to measure the protein levels of calcineurin/nuclear factor of activation T cell (Cn/NFAT) and phosphoinositide 3-kinase/Akt (PI3-K/Akt) . Results: (1) cardiac morphology and structure: the left ventricle was concentric hypertrophy (i.e., cardiac chamber was constricted, ventricular wall was thickened, CSA was increased) and the CVF was increased (P<0.05) in SHR-SED group; the left ventricle was eccentric hypertrophy (i.e., cardiac chamber was dilatated, ventricular wall was thickened) and the CVF was reduced (P<0.05) in SHR-MIIT group; the SHR-HIIT group was eccentric hypertrophy as well, but the cardiac chamber was dilated and ventricular wall was thinner, the CVF was further increased (P<0.05) . (2) cardiac function: the left ventricular ejection fraction (LVEF) was decreased (P<0.05) in SHR-SED group; the LVEF was raised (P<0.05) in SHR-MIIT group but decreased (P<0.05) in SHR-HIIT group compared with SHR-SED group. (3) fetal genes expression: the m RNA levels of ANP, BNP and β-MHC was up-regulated (P<0.05) in SHR-SED group; compared with SHR-SED group, all genes were down-regulated (P<0.05) in SHR-MIIT group while BNP and β-MHC was up-regulated (P<0.05) in SHR-HIIT group. (4) protein expression of cardiac hypertrophy: the CnAβ was increased (P<0.05) and the p-NFATc3/t-NFATc3 ratio was decreased (P<0.05) , but the PI3-K (p110α) and p-Akt/t-Akt ratio showed no significant difference (P>0.05) in SHR-SED group; compared with SHR-SED group, the CnAβ was reduced (P<0.05) , and the p-NFATc3/t-NFATc3 ratio, PI3-K (p110α) and p-Akt/t-Akt ratio were raised (P<0.05) in SHR-MIIT group; in addition, the CnAβ, PI3-K (p110α) and p-Akt/t-Akt ratio were increased (P<0.05) , the pNFATc3/t-NFATc3 ratio was decreased (P<0.05) in SHR-HIIT group. Conclusion: The health effect of long-term interval training on hypertension was dependent on exercise intensity, the MIIT can transform the pathological into physiological hypertrophy to improve the cardiac function, but the HIIT exacerbated cardiac remodeling and accelerate heart failure in SHR. The mechanism was considered to be related to the different regulation of interval training on myocardial collagen metabolism, fetal genes expression as well as the regulation of Cn/NFAT and PI3-K/Akt. Therefore, moderate intensity exercise is still an optimal mode for hypertension patients to rehabilitation in clinical, however, the security and efficiency of HIIT should be further verified.