Renin-angiotensin system (RAS) plays a major role in the development of hypertension in two-kidney, one-clip (2K-1C) hypertensive rats. Asiatic acid exhibits antioxidative, anti-inflammatory and antihypertensive properties in L-NAME hypertensive rats (1). Moreover, Centella asiatica extract, a major source of asiatic acid, inhibits angiotensin converting enzyme (ACE) activity (2). This study, we investigated the effect of asiatic acid and captopril, an ACE inhibitor, on hemodynamic parameters and RAS activity in 2K-1C hypertensive rats. Male Sprague-Dawley rats were anaesthetized with intraperitoneal injection of pentobarbital-sodium (60 mg/kg) and a silver clip (0.2 mm width) was placed on the left renal artery to induce 2K-1C hypertension. 2K-1C hypertensive rats (n = 7/group) were intragastrically administered with vehicle or asiatic acid (30 mg/kg/day) or captopril (5 mg/kg/day) or asiatic acid (30 mg/kg/day) plus captopril (5 mg/kg/day) for six weeks while sham-operated rats (n = 7/group) were treated with vehicle. Systolic blood pressure (SP) was measured weekly using the tail-cuff phletysmography. Rats were anaesthetized as above and then SP, diastolic blood pressure (DP), mean arterial pressure (MAP), heart rate (HR), hind limb blood flow (HBF), and hind limb vascular resistance (HVR) were measured. Angiotensin II type 1 receptor (AT1R) and Angiotensin II type 2 receptor (AT2R) expression in mesenteric arteries and serum angiotensin II (AngII) were examined. All procedures are complied with the standard for the care and use of experimental animals and approved by Animals Ethics Committee of Khon Kaen University. Data are express as mean ± S.E.M which compared by ANOVA. SP was significantly high in 2K-1C hypertensive rats compared to sham-operated rats (201.2 ± 5.7 mmHg vs. 123.4 ± 3.9 mmHg, p<0.001). There were increases in SP, DP, MAP, HR, HVR and a decrease in HBF in 2K-1C hypertensive rats (p<0.001). High serum Ang II level, upreguation of AT1R expression and downregulation of AT2R expression were also seen in hypertensive rats (p<0.05). Asiatic acid, captopril or asiatic acid plus captopril significantly reduced SP (171.1 ± 4, 158.3 ± 5.2 and 151.5 ± 4.8 mmHg, respectively) and improved hemodynamic parameters as well as RAS activation in 2K-1C hypertensive rats (p<0.05). Combined treatment with asiatic acid and captopril showed a greater effect than asiatic acid or captopril alone on hemodynamic parameters (p<0.05). These data suggest that asiatic acid exhibited antihypertensive effect in renovascular hypertensive rats that may associate with their abilities to reduce RAS activation in 2K-1C hypertensive rats. Combined therapy with asiatic acid and captopril produced a synergistic antihypertensive effect.