Butyric acid (BA), a short-chain fatty acid derived from gut microbiota, exhibits beneficial effects on cardiovascular disease. We examined the potential antihypertensive and renal protective action of BA in a mouse model of aldosterone (Aldo)-salt-induced hypertension. C57/BL6 mice were subjected to Aldo-salt protocol consisting of minipump infusion of Aldo at 0.2 mg/kg/d plus 1% NaCl as drinking fluid, or in combination with minipump infusion of BA at 60 mg/kg/d. A 3-wk BA treatment lowered radio telemetry-measured MAP (146±3.8 vs. 133±2.9 mmHg, N=9, p<0.05), cardiac hypertrophy (6.7±0.32 vs. 5.4±0.28 mg/g body weight, N=9, p<0.05), 24-h urinary albumin (434±41vs. 218±22 μg/24h, N=9, p<0.01), the kidney hypertrophy (9.9±0.58 vs. 7.9±0.38 mg/g body weight, N=9, p<0.05), polyuria (19.5 ± 2.5 vs. 8.7±1.4 ml/24h, N=6, p<0.01), renal 8-isoprostane (0.74±0.14 vs. 0.35±0.05 pg/mg, N=6, p<0.05), and urinary TBARS (276±43 vs. 133±032 nmol/24h, N=9, p<0.05). The hematocrit was decreased by Aldo-salt, which was reversed by BA (Control: 50.0±0.4% vs. Aldo-salt: 46.2±0.8% vs. Aldo-salt + BA: 49.6±1.0%, all N=9, all p<0.05). Recent study has identified (pro) renin receptor as a key regulator of blood pressure. To examine the underlying mechanism of BA on Aldo-salt induced effect, we detected full length (pro) renin receptor (fPRR) and soluble PRR (sPRR) expression in vivo and in vitro in this study. The renal expression of fPRR and sPRR were increased 1.75-fold and 2.67-fold by Aldo-salt treatment, respectively, and these increases were both blocked by BA (1.75±0.08 vs. 0.93±0.14, N=6, p<0.01; 2.67±0.23 vs. 0.92±0.29, N=6, p<0.01, respectively). The Aldo-salt induced urinary sPRR excretion was also blunted by BA (Control: 1533±73 vs. Aldo-salt: 4800±365 vs. Aldo-salt + BA: 2615±138 pg/24h, all N=6, all p<0.05). In cultured mpkCCD cells, Aldo treatment induced protein expression of fPRR and sPRR, which were blocked by BA (fPRR: 1.25±0.09 vs. 0.73±0.08, N=5, p<0.01; sPRR: 2.33±0.35 vs. 1.03±0.15, N=5, p<0.01). Our results suggest that BA protected against Aldo-salt-induced hypertension and renal injury likely through suppression of PRR.