Background: Previous studies have demonstrated that elevated homocysteine (Hcy) level represents an independent risk factor for macrovascular disease. However, the relationship between hyperhomocysteinemia and the progression of diabetic retinopathy in patients remains controversial. Hence, the purpose of this systematic review and meta-analysis was to explore any potential association between Hcy and the risk of diabetic retinopathy. Methods: PubMed, Embase, and the Cochrane Library databases were searched to screen studies that fulfilled the inclusion criteria from date of database inception to November 2017. The summary odds ratio (OR) with 95% confidence intervals (CIs) was used to calculate the pooled effect estimate for the relationship between Hcy and diabetic retinopathy risk. Sensitivity, subgroup analyses, and publication bias were also assessed. Results: Eleven studies involving a total of 2184 diabetic patients were included in the meta-analysis. The summary OR suggested that increased Hcy level in diabetic patients was associated with an increased risk of diabetic retinopathy (OR 1.62; 95% CI 1.29-2.03; p < 0.001). Although significant heterogeneity was detected among the included studies, the findings of sensitivity analysis remained statistically significant. Subgroup analyses found a significant association between Hcy and diabetic retinopathy in most subsets, but no significant association was found if the sample size was < 100, participants had type 1 diabetes mellitus, and the study quality was low. Conclusions: The findings of this study suggested that elevated Hcy level was associated with an increased risk of diabetic retinopathy, especially in type 2 diabetic patients. This finding may help diabetic patients to achieve effective management strategy to prevent the progression of diabetic retinopathy.