Objective To observe the effects of arginine vasopressin V2 receptor (AVP V2R) antagonist on water and sodium retention of adriamycin-induced nephropathy rats and to explore its mechanism. Methods Nephropathy was induced by intravenous injection of ADR. The rats were divided into 4 groups: untreated adriamycin nephropathy group(NS group), Adriamycin nephropathy group treated by AVP-V2R antagonist (V group, 42 μg·kg -1·d -1, by subcutaneous injection), Adriamycin nephrotic group treated by fosinopril (F group, 25 mg·kg -1·d -1 by gavage) and normal control group (NC group). The interventions continued for 4 weeks. Plasma sodium, osmolality, urinary osmolality and urinary sodium excretion were measured at the end of the study. Immunohistochemistry and Western Blot were used to detect the expression of AQP2, AQP3 and AVP V2 receptor in the kidney. RT-PCR was used to examine the AQP2 mRNA, AQP3 mRNA and AVP V2 receptor in the kidney. Results ①Increased plasma osmolality and plasma sodium in nephropathy rats were ameliorated and urinary osmolality and urinary sodium excretion were increased by AVP V2R antagonist. ②AVP V2R antagonist decreased the expression of AVP V2R protein in the kidney. ③Compared with the untreated NS rats, the expression of AQP2 mRNA in the kidney increased and the expression of AQP2 protein in the kidney decreased in AVP-V2R antagonist treated rats. At the same time, compared with the untreated nephropathy rat, the expression of APQ3 decreased in AVP V2R antagonist treated rats. Conclusion AVP V2R antagonist mitigates water and sodium retention of Adriamycin nephropathy rats by changing the expression of AQP2 and AQP3 in the kidney.