Abstract: Background: By inhibiting xanthine oxidase, subsequent inflammatory cytokine release and the resulting breakdown of the blood-retina barrier, allopurinol may limit the inflammation-driving diabetic macular edema (DME). Methods: We examined the relationship between allopurinol and DME among type 2 diabetic United States veterans using a retrospective cohort study. We used propensity score matching and Cox hazard models to estimate the risk of DME. Results: Propensity score-matched Cox models revealed allopurinol was associated with a 24.6% reduction in the risk of DME (HR = 0.754; 95% CI = (0.684-0.831)). Conclusion: Allopurinol could reduce the risk of DME, one of the major causes of visual disturbance among diabetic patients. Further research into the effects of allopurinol on DME is warranted.