The aim of the present study was to investigate the effect of Mushroom Insoluble Non-Starch Polysaccharides (MINSP) on Ochratoxin A-induced hepato-renal damage in rat. MINSP (75 and 150 mg/kg) administered daily for 15 days in concomitantly with Ochratoxin A (OA) (1.7 mg/Kg), Intraperitoneal (i.p). Normal groups treated with MINSP showed significant decrease in serum levels of Î³-Glutamyle Transferase (GGT), Aminotransferases (ALT & AST), creatinine, uric acid, total antioxidant capacity (TAC), Tumor Necrosis Factor Alpha (TNF-Î± ) and Carcinoembryonic Antigen (CEA). In liver and kidney homogenates there were significant decreases in Malonaldehyde (MDA), and Nitric Oxide (NO); while Superoxide Dismutase (SOD) content increased after treatment with MINSP. OA-treated rats showed significant elevation in serum ALT, AST, TNF-Î±, CEA, Uric acid , creatinine, MDA and NO and reduction of SOD level in hepatic and renal tissues. The combined treatment with MINSP+OA significantly ameliorated the tested parameters when compared with OA-treated group. It improved the antioxidant activity of the liver and kidney in dose-dependent manner.