AIM: To examine the ocular toxicity linked to sildenafil usage and the possible protective benefits of adenosine triphosphate (ATP) against this toxicity in rats. METHODS: Twenty-four male albino Wistar-type rats were divided into four equal groups (n=6/group) as follows: healthy group (HG), ATP-only group (ATPG), sildenafil-only group (SILG), and ATP+sildenafil group (ATP+SLD). ATPG and ATP+SLD groups were injected intraperitoneally with ATP (4 mg/kg), while SILG and HG groups were injected with saline (0.9% NaCl) by the same route as a solvent. One hour after the administration of ATP and solvent, sildenafil (10 mg/kg) was administered orally to the SILG and ATP+SLD groups. This procedure was repeated once a day for 4wk. The animals were then sacrificed, eyeballs were removed and oxidant and antioxidant parameters were measured biochemically. Additionally, the ocular tissues were evaluated histopathologically. RESULTS: Sildenafil increased oxidant (malondialdehyde) levels and decreased antioxidant levels (total glutathione, superoxide dismutase, catalase) in rat ocular tissues and caused severe oxidative stress. In addition, sildenafil has been shown histopathologically to cause oxidative damage in retinal layers. ATP treatment suppressed oxidative stress and attenuated histopathological damage in the retinal layers. CONCLUSION: ATP protects retinal tissue against sildenafil-induced ocular oxidative damage in rats and may contribute to the development of novel approaches to prevent or treat this damage.