Purpose: Cortical cataracts commonly occur in people with presbyopia and may be due to age-related loss of accommodation. Wedge-shaped or spoke-like opacities develop underneath insertion points of lens zonules, suggesting a possible link between lens zonular tension and cortical cataracts. Previous studies have suggested an association between accommodative stress and formation of cortical cataracts. We tested the hypothesis that increasing the tension of lens zonules by paralyzing ciliary muscles with cycloplegic drugs may promote cortical cataractogenesis. Methods: Diabetic rats were treated with cycloplegic eye drops (atropine or cyclopentolate) to paralyze the ciliary muscles and produce lens zonular tension. Lens opacification, diffusion of fluorescein into the lenses, and protein leakage into aqueous humor, were assessed at various time points. For human comparison, visual accommodative amplitude data from patients with cortical cataracts as well as agematched normal controls were collected and analyzed. Results: Atropine and cyclopentolate-treated diabetic rats developed lens opacities earlier and with greater severity than diabetic control rats. Fluorescein diffusion into the lens, and leakage of proteins in the aqueous in atropine-treated diabetic eyes was significantly higher than in diabetic controls, and undetectable in nondiabetic controls. Clinical data showed significantly lower visual accommodative amplitude in cortical cataract patients than in normal controls. Conclusion: Chronic use of cycloplegic drugs that paralyze ciliary muscles and increase lens zonular tension can accelerate lens leakage and opacification, contributing to formation of cortical cataracts. Clinical and experimental data support the hypothesis that increased lens zonular tension, which can be associated with presbyopia and clinical pupillary dilation, may promote cortical cataractogenesis.