BACKGROUND Sorbitol-aldose reductase (polyol) pathway genes have been strongly linked to diabetic retinopathy. Polymorphisms in these genes may affect their functions and influence the risk of retinopathy. In this work, we investigated the influence of the rs759853 polymorphism of ALR2 gene and rs2055858 and rs3759890 polymorphisms of SDH gene on risk of diabetic retinopathy among Han Chinese. MATERIAL AND METHODS We included 3,000 subjects in our study, of which 1,500 were patients with diabetic retinopathy and 1,500 were controls without the said condition. Among the cases, 750 had the non-proliferative diabetic retinopathy (NPDR) and 750 had proliferative diabetic retinopathy (PDR). The polymorphisms were genotyped using established methods and logistic regression analysis was used to determine whether the polymorphisms were associated with risk of diabetic retinopathy. RESULTS We found that variants of ALR2 rs759853 polymorphism were significantly associated with an increased risk of diabetic retinopathy, whereas variants of SDH rs2055858 polymorphism were significantly associated with a lower risk. For the former, an odds ratio (OR) of 1.46 were noted for the heterozygous genotype (95% CI=1.25-1.70, P<0.01) and the homozygous variant genotype (OR=1.90, 95% CI=1.40-2.60, P<0.01). For SDH rs2055858 polymorphism, an OR of 0.51 (95% CI=0.43-0.61, P<0.01) and 0.34 (95% CI=0.28-0.42, P<0.01) was observed for heterozygous and homozygous variant genotype respectively. Subgroup analysis based on NPDR and PDR showed a similar finding as the combined results. CONCLUSIONS ALR2 rs759853 and SDH rs2055858 polymorphisms were respectively associated with a higher and lower risk of diabetic retinopathy.