Abstract: Objective To investigate the changes in renal sodium transport during development of hypertension in ouabain-hypertensive rats (OHR) and further elucidate the role of ouabain in the pathogenesis of hypertension. Methods Eighty male SD rats weighing 80-100 g were randomized equally into normal control and ouabain groups and treated with intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 μg/kg) once daily, respectively. Systolic blood pressure (SBP) and body weight of the rats were recorded weekly. One week before sacrifice scheduled at weeks 2, 4, 6 and 8, respectively, the rats were individually housed in metabolic cages to determine food consumption twice. Blood and 24-hour urine samples were collected to measure serum and urine concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the distal tubules (FDRNa) were calculated. Results The body weight and food intake between ouabain groups and control groups were comparable during the experiment (P>0.05). Blood pressure was also comparable in the two groups after 2 weeks (P>0.05). At week 4, however, blood pressure of ouabain group was significantly higher than that of the control group (P<0.001) and increased in a dose-dependent manner. The SBP in ouabain group appeared to reach a plateau at week 7. Ccr and plasma sodium(PNa) were similar in the 2 groups during the experiment (P>0.05). FELi was significantly lower at weeks 2, 4 and 6 in ouabain group than in the control group (P<0.01), and FELi decrement in ouabain group was accompanied by reduced sodium excretion. FENa was significantly lower at week 4 in ouabain group than in the control group (P<0.05), but this difference was not significant in weeks 2 and 6 (P>0.05). At weeks 2, 4 and 6, ouabain group showed significantly lower FDRNa than the control group (P<0.05), suggesting the compensation of the distal nephron segments. After 8 weeks, FENa, FELi and FDRNa were similar between the two groups (P>0.05). Conclusions Ouabain can increase renal proximal tubule reabsorption of sodium and consequently decrease renal sodium excretion in OHR, which can contribute to alteration of the pressure-natriuresis relationship in OHR, and play an important role in the development and maintenance of hypertension of OHR.