There is concern that environmental estrogens are causing reduced sperm counts in humans and dwindling wildlife populations. The objective of this randomized, controlled study was to determine if lycium barbarum polysaccharide (LBP) extracted from Gou Qi Zi (Lycium) has protective effects against diethylstilbestrol (DES) induced testicular damage. Forty-eight hamsters were randomly divided into 6 groups of 8 hamsters each. A control group received no DES and the other 5 groups received DES (1.0 mg/kg) subcutaneously alone or combined with LBP or vitamins for 7 consecutive days. Three groups received a daily gavage of LBP 1, 10 or 50 mg/kg respectively. The final DES group received a gavage of vitamin C (100 mg/kg) and vitamin E (200 IU/kg) daily. Testicular weight, histopathology and superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and malondialdehyde (MDA) levels were evaluated. The DES group had atrophy of the testis, damage to the seminiferous tubules and decreased antioxidant potency. Supplementation with LBP (10 or 50 mg/kg) attenuated the DES testicular toxicity and testicular weights and morphology were significantly better than with DES alone. The testicular SOD and T-AOC were also significantly increased and the levels of MDA significantly decreased, compared to DES alone. Vitamins C and E showed a similar testicular protective effect against DES toxicity. In conclusion LBP (10 or 50 mg/kg) has a protective effect against testicular DES toxicity in hamsters. Further studies are warranted to determine if LBP and Gou Qi Zi (Lycium) will prevent reproductive dysfunction associated with low-level environmental estrogens.