The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium sensitive hypertension following recovery from ischemia reperfusion (I/R) induced acute renal failure. Male Sprague-Dawley rats fed 0.4% NaCl chow were subjected to 40 minute bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0% NaCl chow for 28 days and administered vehicle or MMF (20 mg/kg/day, ip). High salt mean arterial pressure (MAP) was significantly higher in I/R rats (144±16 mmHg) compared to vehicle treated sham rats (122±2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114±3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27±0.07 ml/min/100gbwt) compared to vehicle-treated sham rats (0.58±0.04 ml/min/100gbwt); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64±0.07 ml/min/100gbwt). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.