Adult male Fisher344 rats were randomized into five groups (n=6–8 in each group): Olive oil, Cyclosporine (15mg/kg/day), Cyclosporine + DPI (15mg/kg/day CsA + 0.5mg/kg/day), Cyclosporine + DPI (15mg/kg/day CsA + 1.0mg/kg/day) or Cyclosporine + Apocynin (15mg/kg/day + 16mg/kg/day). They received treatment for 30 days. Trichrome (a,b) studies demonstrated the typical striped fibrosis and cytoplasmic vacuolization that characterize chronic CNI toxicity. Immunoperoxidase studies showed that CsA nephrotoxicity was associated with upregulation of Nox2 (brown) in tubular and interstitial cells, and interstitial upregulation of α-SMA (purple) (c, d).