Abstract: OBJECTIVE To study the protective effect and mechanism of Astragalus polysaccharide(APS) on cardiac remodeling. METHODS Mouse cardiac remodeling model prepared by transverse aortic constriction(TAC) was treated with APS. The protective effect of APS on cardiac remodeling was evaluated by echocardiography, wheat germ agglutinin staining and picrosirius red staining of myocardial tissue and Real-time PCR. Expression level of Nox4, TGF-β1, mTOR and Akt was detected by Western blotting to illustrate the mechanism of APS on cardiac remodeling. RESULTS After TAC for 4 weeks, compared to blank control group, left ventricular end-diastolic posterior wall dimension(LVPWd) was significantly increased(P<0.01), the contractile function of the left ventricle decreased significantly, and the LVPWd of the mice in the APS+TAC group was significantly lower than that in the TAC group(P<0.05), and the contractile function of the left ventricle was significantly improved. APS treatment could inhibit TAC-induced increase in ratio of heart weight to body weight and heart weight to tibial length(P<0.001). The pathological staining results of myocardial tissue showed that a significant increase in cardiac hypertrophy and fibrosis was found in mice in TAC group compared with blank control group(P<0.01), while APS treatment had a significantly protective effect on TAC-induced cardiac hypertrophy and fibrosis(P<0.01 or P<0.05). Compared to blank control group, a significant increased expression level of atrial natriuretic peptide and brain natriuretic peptide were observed in heart of model mice(P<0.001), which was inhibited in APS-treated mice(P<0.01 or P<0.05). Further study showed that APS had a significant inhibitive effect on TAC-induced expression of Nox4, TGF-β1, mTOR and p-Akt in myocardial tissue. CONCLUSION APS protect TAC-induced cardiac remodeling via inhibiting TGF-β1 and Nox4/Akt/mTOR signal pathway.