AIM: To investigate the association of Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism with diabetic retinopathy (DR). METHODS: PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Subgroup, sensitivity, and cumulative analyses were performed. Publication bias was also analyzed. RESULTS: Eight studies were included in the pooled analysis. The MnSOD Val16Ala polymorphism was associated with the risk of DR under the dominant model (OR=0.66, 95%CI=0.48-0.91, P<0.0001), this result was demonstrated to be relatively stable in cumulative analysis. No significant publication bias was found. This polymorphism was also associated with the risk of DR in Caucasians under the dominant model (OR=0.64, 95%CI=0.42-0.97, P=0.04,) and in Asians under the recessive model (OR=0.31, 95%CI=0.11-0.88, P=0.03). CONCLUSION: These findings suggest that the MnSOD Val16Ala polymorphism is a risk factor for DR, and that more attention should be paid to carriers of these susceptibility genes.