Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used medications because they provide effective relief of chronic pain and inflammation through inhibition of cyclooxygenase (COX). However, visual side effects also have been reported, such as temporary blindness, visual field defect, blurred vision, scotomata, and color vision changes subsequent to short- or long-term use. Our aim was to investigate the effect of a high dose of meclofenamic acid (MFA) on the retina. In our study, we applied electroretinography (ERG) and histologic examination to study functional and morphological damage of the retina in rabbits after MFA treatment. We reveal that MFA markedly decreased the amplitudes of b-wave of Rod-response and a- and b-wave of the scotopic standard combined ERG, respectively, and induced morphological destruction of the retina, especially photoreceptor cells. We conclude that a high dose of MFA causes retinal toxicity and impairs visual transduction. These findings may explain, at least partially, the vision problems of certain clinically used NSAIDs.