Abstract: Cisplatin (CDDP) is a potent anticancer agent associated with a variety of toxicities. The present study was carried out to investigate the cytoprotective and antioxidant activities of silymarin (SIL) on CDDP induced toxicity. Hepatotoxicity was manifested biochemically from increased activities of Aspartate Transaminase (AST), Alanine Transaminase (ALT), glucose concentration in serum, a markedly increased level of liver lipid peroxidation (malondialdehyde, MDA) associated with significantly reduced activities of the antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GPx) in CDDP group. CDDP induced histochemical alterations including: a significant depletion in glycogen stores, total protein and DNA contents in liver cells. On the other hand, post-treatment with SIL significantly decreased serum liver markers, MDA levels and increased SOD and GPx activities and mild histochemical damage than those receiving CDDP. Results suggest that pretreatment with SIL could protect liver tissues fully against CDDP toxicity, since liver markers, MDA levels; activities of antioxidant enzymes and glycogen, protein and DNA contents in liver cells were restored to normal levels. In conclusion, the cytoprotective potential of SIL in CDDP toxicity might be due to its antioxidant, metal chelating property and free radical scavenging properties, which could be useful for achieving optimum effects in CDDP induced hepatotoxicity.