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Background and purpose: MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression. MiRNA‐126 and miRNA‐146a have been described as having abnormal expressions in diabetic retinopathy (DR) patients. Polymorphisms in genes codifying miRNAs (miRSNPs) may alter the expression of the corresponding miRNA and, thus, interfere with susceptibility to DR. Therefore, miRSNPs in miR‐126 and miR‐146a genes could be associated with DR susceptibility. The purpose of this study was to investigate the association between miR‐126 rs4636297 (G/A) and miR‐146a rs2910164 (G/C) miRSNPs and DR. Methods: This case–control study included 195 type 1 diabetes mellitus (T1DM) patients with DR (cases) and 215 patients without DR and with ≥10 years of T1DM (controls). MiRSNPs were genotyped by real‐time PCR. Results: Genotype distributions of two analysed miRSNPs were in Hardy–Weinberg equilibrium in controls (p > 0.050). Frequencies of the miR‐126 rs4636297 miRSNP were not significantly different between case and control groups (p = 0.169). However, after adjustment for age, glycated haemoglobin, triglycerides, estimated glomerular filtration rate and ethnicity, the A allele of this miRSNP was associated with protection for DR under additive [OR: 0.444 (95% CI: 0.211–0.936), p = 0.033] and dominant [OR: 0.512 (95% CI: 0.303–0.865), p = 0.012] inheritance models. Genotype and allele frequencies of miR‐146a rs2910164 miRSNP did not differ between groups (p = 0.368 and p = 0.957), and this polymorphism was not associated with DR when assuming different inheritance models. Conclusion: Our results suggest an association between the A allele of miR‐126 rs4636297 miRSNP and protection for DR in a Southern Brazilian population. [ABSTRACT FROM AUTHOR]