The diuretic effect of Astragali Radix (AR) in humans was described in ancient books, but its mechanism has not been identified. To evaluate its diuretic/natriuretic effect, we conducted a double-blind, randomized, crossover study in 12 healthy men. They were randomized to receive either placebo (n=6) or a single oral dosage of 0.3g/kg body weight of aqueous extract of AR (ARE) (n=6). Compared with placebo, ARE treatment markedly increased urinary sodium excretion (U(Na)V), fractional sodium excretion, and urinary excretion of chloride during the first 4h. No significant changes of these parameters were observed during 12h or 24h. ARE elevated plasma ANP (pANP), urinary excretion of cGMP (U(cGMP)V) and U(cGMP)V/pANP ratio without affecting plasma level of rennin-angiotensin-aldosterone system, mean arterial blood pressure and glomerular filtration rate. The change in U(Na)V was closely correlated with pANP, U(cGMP)V, and U(cGMP)V/pANP ratio. In addition, the seven volunteers who presented marked natriuresis did not show higher level of plasma Astragaloside IV than the other five volunteers. We first demonstrate that ARE induces a marked natriuresis in healthy men, which is attributed to enhanced renal responses to endogenous ANP. The Astragaloside IV in the ARE is not the active component for natriuresis.