This study was performed in order to determine the effectiveness of Rho kinase inhibitor and nuclear factor kappa beta (NFkB) inhibitor in renal injury of angiotensin II-infused hypertensive rats. Male Sprague-Dawley rats, maintained on a normal diet, received either a sham operation (N=7) or continuous angiotensin II infusion (120 ng/min) subcutaneously via minipumps. The angiotensin II-infused rats were further subdivided into 3 subgroups (N=7 each) to receive one of the following treatments during the entire period: vehicle, Rho kinase inhibitor (Fasudil, 3 mg/kg/day, intraperitoneously), or NFkB inhibitor (Parthenolide, 1 mg/kg/day, intraperitoneously). After 12 days of angiotensin II infusion, systolic blood pressure (BP, 208+/-7 vs 136+/-3 mmHg), Rho kinase activity, NFkB activity, renal angiotensin II contents (160+/-25 vs 84+/-14 pg/g), monocytic chemotactic protein (MCP) 1 mRNA, interstitial macrophage infiltration, transforming growth factor beta (TGFb) 1 mRNA, interstitial collagen-positive area, urinary protein excretion (43+/-6 vs 11+/-2 mg/day), and urinary albumin excretion were significantly enhanced compared to the Sham group. While Fasudil or Parthenolide did not alter systolic BP (222+/-8 and 190+/-21, respectively), both treatments completely blocked angiotensin II-induced enhancement of NFkB activity, renal angiotensin II contents (103+/-11 and 116+/-21, respectively), MCP1 mRNA, interstitial macrophage infiltration, TGFb1 mRNA, interstitial collagen-positive area, urinary protein excretion (28+/-6 and 23+/-3, respectively), and urinary albumin excretion. Importantly, Parthenolide did not alter angiotensin II-induced Rho kinase activation although Fasudil abolished angiotensin II-induced Rho kinase activation. These data indicate that Rho - NFkB axis plays crucial roles in the development of angiotensin II-induced renal injury independently from BP regulation.