Introduction: Cisplatin is an antineoplastic agent which is used in treatment of various cancers. However its clinical use is associated with oxidative stress-mediated neuropathic pain. This research aimed to explore the effect of silymarin on cisplatin-induced hyperalgesia (CIH) and oxidative stress biomarkers in male rats. Methods: Fifty-six male rats were allocated into seven equal groups. Hyperalgesia was caused by intraperitoneal single dose administration of cisplatin (1mg/kg) and assessed by utilizing tail-flick method. The impact of silymarin (25, 50 and 100 mg/kg/day for 15 days) on CIH was investigated on days 1, 5, 10 and 15. Blood samples were collected to assess malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) and total antioxidant status (TAS) on day fifteen. Results: Single dose injection of cisplatin (1mg/kg) could cause a significant hyperalgesia on days 5, 10 and 15. CIH was abolished by daily administration of silymarin (50 and 100mg/kg) on days 10 and 15. Serum MDA level was decreased in cisplatin and silymarin (100 mg/kg) co-treated rats, while there was an increase in GPx, SOD as well as TAS parameters. Conclusion: The results of this study revealed that silymarin prevents from CIH possibly by improving lipid peroxidation and oxidative stress biomarkers. Other clinical studies should be performed to establish possible use of silymarin for treatment of CIH in susceptible individuals.