Abstract: Objective: To investigate the therapeutic effect of Qiangxinkang, the traditional Chinese medicine prescription,on chronic heart failure (CHF) rats,and to explore its relationship with the arginine vasopressin (AVP)- V2 receptor (V2R)-cyclic adenosine monophosphate (cAMP)-aquaporin 2 (AQP2) signaling pathway. Methods: Among 50 SPF-grade Wistar rats, 10 were randomly selected as the blank group, and the remaining 40 rats were used to establish CHF models by intraperitoneal injection of Doxorubicin. After excluding rats that failed to model or died, the remaining model rats were divided into model group, Qiangxinkang high-dose group, and Qiangxinkang low-dose group, with 10 rats in each group. The blank group and model group were intragastrically administered 10 mL/kg distilled water, while the Qiangxinkang high-dose and low-dose groups were intragastrically administered Qiangxinkang solution at doses of 23.5 g(/ kg·d) and 5.89 g(/ kg·d),respectively,at a volume of 10 mL/kg. Changes in urine output,urinary sodium excretion rate,and body weight of each group were recorded. Echocardiography was used to observe changes in fractional shortening (LVFS) and ejection fraction (LVEF) of the left ventricular. Western blot was performed to detect the expression of V2R and AQP2 in rat renal tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of AVP and cAMP in serum and renal tissues. Results:Compared with the blank group,the model group showed no significant increase and even decreased in body weight (P<0.05), decreased urine output and urinary sodium excretion rate (P<0.05), decreased LVFS and LVEF of the left ventricular (P<0.05), increased expression of V2R and AQP2 proteins in renal tissues (P<0.05), and increased levels of AVP and cAMP in serum and renal tissues (P<0.05). Compared with the model group, the Qiangxinkang high-dose and low-dose groups showed increased urine output (P<0.05) and increased urinary sodium excretion rate (P<0.05). The Qiangxinkang high-dose group showed increased LVFS and LVEF of the left ventricular on echocardiography (P<0.05). The relative expression levels of V2R and AQP2 proteins in renal tissues were decreased in the Qiangxinkang high-dose group (P<0.05). The relative expression level of AQP2 protein in renal tissues was decreased in the Qiangxinkang low-dose group (P<0.05),while the relative expression level of V2R protein showed a decreasing trend but without statistical significance (P>0.05). The levels of AVP and cAMP in serum and renal tissues were decreased in the Qiangxinkang high-dose group (P<0.05). The levels of AVP and cAMP in renal tissues were decreased in the Qiangxinkang low-dose group (P<0.05), while the levels of AVP and cAMP in serum showed a decreasing trend but without statistical significance (P>0.05). Conclusion:Qiangxinkang can regulate water-sodium metabolism and improve cardiac systolic function in CHF rats by inhibiting the AVP-V2R-cAMP-AQP2 signaling pathway.