Activation of the renin-angiotensin system (RAS) contributes to the progression of chronic kidney disease (CKD). Based on the known cellular effects of angiotensin II to promote inflammation, we posited that stimulation of lymphocyte responses by angiotensin II might contribute to the pathogenesis of hypertensive kidney injury. We therefore examined the effects of the immunosuppressive agent mycophenolate mofetil (MMF) on the course of hypertension and kidney disease induced by chronic infusion of angiotensin II in 129/SvEv mice. Although it had no effect on the severity of hypertension or cardiac hypertrophy, treatment with MMF significantly reduced albuminuria and ameliorated kidney injury, decreasing glomerulosclerosis and reducing lymphocyte infiltration into the renal interstitium. Attenuation of renal pathology with MMF was associated with reduced expression of mRNAs for the pro-inflammatory cytokines interferon-g and tumor necrosis factor-a and the pro-fibrotic cytokine transforming growth factor-. As infiltration of the kidney by T lymphocytes was a prominent feature of angiotensin II-dependent renal injury, we carried out experiments examining the effects of angiotensin II on lymphocytes in vitro. We find that exposure of splenic lymphocytes to angiotensin II causes prominent rearrangements of the actin cytoskeleton. These actions require the activity of Rho kinase. Thus, angiotensin II exaggerates hypertensive kidney injury by stimulating lymphocyte responses. These pro-inflammatory actions of angiotensin II seem to have a proclivity for inducing kidney injury while having negligible actions in the pathogenesis of cardiac hypertrophy.