IntroductionDoxorubicin (DXR), a chemotherapeutic antibiotic, is widely used as an anticancer drug in clinics. Grape seed extract is known for its potent antioxidant properties. The aim of this study is to investigate the effect of high-antioxidant content Vitis vinifera L. seed extract against DXR-induced testicular and epididymal damage.Methods30 male rats were randomly divided into five groups with six animals in each group: Control, Sham, DXR (a single i.p. dose of 15 mg/kg), DXR + VIT (120 mg/kg VIT seed extract via gavage for 14 days and a single i.p. dose of DXR (15 mg/kg) on day 5, VIT (120 mg/kg VIT seed extract via gavage for 14 days). Animals were sacrificed under anesthesia 24 hours after the last drug administration, and blood, testis, and epididymis tissues were collected.ResultsTissues from the DXR group exhibited atrophic seminiferous tubules, Leydig cell degeneration, tunica albuginea and basal membrane thinning, immature spermatogenic cells, vascular congestion, epididymal atrophy, epithelial cell deletion, decreased sperm count, increased connective tissue, and absence of sperm in the lumen. Serum levels of interleukin 6 (IL-6), interleukin 1β (IL-1β), Tumor Necrosis Factor