Abstract: Objective To explore the cardioprotective effect and mechanism of astragaloside Ⅳ（AS-Ⅳ） on angiotensin Ⅱ（AngⅡ） induced hypertension rat model. Methods Sixty Sprague-Dawley（SD） rats were randomly divided into 6 groups, with 10 rats in each group: control group, model group, AS-Ⅳ low dose group（10 mg/kg）, AS-Ⅳ medium dose group（20 mg/kg）, AS-Ⅳ high dose group（50 mg/kg） and specific inhibitor of ADP-ribosylation factor 6（Arf6）（NAV-2729） group. Rats were treated with different drugs or doses after AngⅡ-induced hypertensive myocardial injury models were established. The left ventricular end-diastolic diameter, cardiac ejection fraction and fractional shortening, myocardial pathological injury, myocardial apoptosis and the expression of related apoptotic proteins Bcl-2（B-cell lymphoma-2） and Bax（Bcl-2 associated X） in each group were observed after 2 weeks. The other 30 SD rats were randomly divided into three groups, with 10 rats in each group: chloride intracellular channel protein 4（CLIC4） overexpression combined with AS-Ⅳ group, adenovirus negative control combined with AS-Ⅳ group and adenovirus negative control group. The rats were injected with corresponding adenovirus by tail vein and then AngⅡ-induced hypertensive model was eatablished. The end-diastolic internal diameter of the left ventricle, left ventricular ejection fraction, fractional shortening, myocardial pathological damage, and myocardial apoptosis were observed after 2 weeks. Results Compared with the model group, the middle dose and high dose of AS-Ⅳ could improve the cardiac function and myocardial structure of AngⅡ-induced hypertensive myocardial injury model rats, promote the expression of anti-apoptotic protein Bcl-2（0.36±0.01 vs 0.22±0.02, 0.78±0.01 vs 0.22±0.02; both P＜0.05） and inhibit the expression of Bax（1.51±0.02 vs 2.13±0.03, 1.22±0.01 vs 2.13±0.03; both P＜0.05）. AS-Ⅳ exerted myocardial protective effect by inhibiting the expression of CLIC4/Arf6 protein, and overexpression of CLIC4 attenuated this protective effect. Conclusion AS-Ⅳ can ameliorate myocardial injury in AngⅡ-induced hypertension rat model, possibly through inhibiting CLIC4/Arf6 signaling pathway.