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Background: Side effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use. Instead, evidence indicates that crocin (CR) has synergistic anti-cancer potential with CIS and exhibited beneficial effects on CIS-induced hepatorenal damage. The aim of this study was to investigate the protective potential of CR against CIS-induced testicular toxicity in rats., Methods: Fifty adult male Wistar rats randomly assigned to five equal groups including control, CIS, and CIS plus CR at doses of 6.25 mg/kg (CIS + CR6.25), 25 mg/kg (CIS + CR25), and 100 mg/kg (CIS + CR100). CIS and CIS + CR groups received a single intraperitoneally (i.p.) injection of CIS (7 mg/kg). CR (6.25-100 mg/kg i.p.) injections were started three days before the CIS injection and continued once a day for up to 13 days. On the 14th day, all animals were sacrificed and their blood samples and testes were removed for biochemical and histological analyses., Results: Compared to the control group, CIS significantly decreased relative testis weight (0.28 vs. 0.39, p < 0.001), testosterone level (0.3 vs. 2.31 ng/mL, p < 0.001), germinal layer area (25,886 vs. 35,320 µm 2 , p < 0.001), superoxide dismutase (SOD) (0.9 vs.1.73 U/mg, p < 0.001) and increased testicular lipid peroxidation (3.05 vs. 15.35 nmol/mg, p < 0.001). CR at 25 mg/kg ameliorated testicular lipid peroxidation and enhanced SOD activity compared to CIS group (p < 0.05). Besides, CR treatment at the maximum dose (100 mg/kg) resulted in reversing CIS effects on testis weight, testosterone level, SOD, lipid peroxidation, and germinal layer area., Conclusions: These findings demonstrated that CR co-treatment could prevent CIS-induced testicular toxicity in rats., (© 2021. The Author(s).)