The association of angiotensin-converting enzyme (ACE) gene polymorphism with diabetic retinopathy (DR) was investigated in many studies with conflicting results. To shed light on these inconclusive findings, a meta-analysis of all available studies relating I (insert)/D (delete) polymorphism to the risk of developing DR was conducted. This meta-analysis included genotype data on 2,342 cases with DR and 2,048 controls free of DR. Summary odds ratios were estimated. Potential sources of heterogeneity and bias were explored. Overall, in allelic genetic model, heterogeneity between studies was nonsignificant (P = 0.12). No publication bias was observed in the regression asymmetry test (tau = 0.84, P = 0.41). There was no significant association between this variant and DR. In additional analysis, the association of I/D variant with retinopathy was nonsignificant both in patients with type 1 diabetes (T1D) (1.01 [95% CI: 0.79-1.29]) and in patients with type 2 diabetes (T2D) (1.12 [95% CI: 0.93-1.35]). Significant association was not also observed between I/D variant and the background diabetic retinopathy (BDR). For the I/D polymorphism and its relationship to proliferative diabetic retinopathy (PDR), the dominant model showed nonsignificant heterogeneity among studies (P = 0.52; I-2 = 0%), and the fixed estimate pooled odd ratio (OR) JOPwas significant, at 1.37 [95% CI: 1.02-1.84]. No association was observed between ACE I/D variant and DR, irrespective of the diabetic type. There was moderate evidence of its relationship to PDR, while its relationship to BDR was not found. Studies exploring the association between ACE I/D polymorphism and BDR or PDR may help us better understand the genetics of DR.