Cisplatin causes renal fibrosis, but the development mechanism of interstitial fibrosis is not yet understood. We examined the effect of nano form antioxidant, N, N'-diphenyl-1, 4-phenylenediamine (Nano-DPPD), on development of interstitial fibrosis induced by cisplatin. Cisplatin increased blood urea nitrogen (BUN), serum creatinine, serum magnesium and serum chemoattractant protein (MCP-1) on the other hand it decreased creatinine clearance levels. Also administration of cisplatin made many pathological abnormalities represented in increasing collagen deposition, α-smooth muscle actin, Ki67 and renal tubular injury. Administration of Nano-DPPD, which was started at 3 days after cisplatin treatment, significantly inhibited the increase in renal collagen contents and the expansion of the interstitial fibrosis area. These results indicate that anti-fibrotic action of Nano-DPPD is not secondary due to the inhibition of acute renal injury but is rather a direct effect on renal fibrogenesis. Nano-DPPD prevent the infiltration of macrophages by cisplatin, suggesting that anti-fibrotic action of Nano-DPPD was not mediated by the inhibition of inflammatory cellular influx. It is suggested that reactive oxygen species and collagen deposition are involved in cisplatin-induced renal interstitial fibrosis.