Objective To investigate the effects of valsartan on sarcoplasmic reticulum calcium adenodine triphosphatase expression and function in a rabbit model of heart failure. Methods Twenty-seven rabbits were divided into sham-operated, heart failure and valsartan groups, with 9 in each group. The rabbit model of heart failure was prepared by volume overload plus pressure overload. After 7 weeks, left ventricular function, hemodynamic parameters, and expression and function of SERCA2 were observed. Results Compared with sham-operated rabbits, left ventricular mass index (LVMI)and left ventricular end diastolic pressure (LVEDP)were significantly increased in heart failure rabbits [(1.32±0.06)vs (3.61±0.09)g/kg and (?0.50±1.05)vs (23.00±2.37)mmHg respectively, P＜0.05], but the left ventricular shortening fraction and left ventricular ejection fraction (LVEF)were significantly decreased in heart failure rabbits [(37.83±3.58)% vs (17.38±3.13)%; (72±5)% vs (38±6)%, P＜0.05]. Compared with heart failure rabbits, LVMI and LVEDP were significantly decreased in valsartan rabbits [(2.07±0.14)g/kg and (2.17±0.72)mmHg respectively, P＜0.05], but their left ventricular shortening fraction and LVEF were increased [(33.8±2.9)% and (65±4)% respectively, P＜0.05]. Expression and function of SERCA2 were remarkably lower in heart failure rabbits than in sham-operated rabbits [(0.69±0.04)vs (1.02±0.02)and (54.4±7.9)% vs (95.5±2.1)% respectively, P＜0.05], while compared with heart failure rabbits, they were significantly higher in valsartan rabbits [(0.91±0.02)and (81.7±4.9)% respectively, P＜0.05)]. Conclusion Valsartan can improve cardiac function, probably owing to its roles in upregulating expression and function of SERCA2 in the prevention of heart failure.