AbstractThe transforming growth factor beta 1 (TGFB1) is a pro-inflammatory cytokine that plays a key role in the mechanisms of angiogenesis and breakdown of the blood-retina barrier, which are implicated in the pathogenesis of diabetic retinopathy (DR). Polymorphisms in theTGFB1gene have been associated with DR; however, results are still contradictory. Therefore, the aim of this study was to investigate the potential association between twoTGFB1polymorphisms and DR. This study included 992 patients with diabetes mellitus (DM): 546 patients with DR (cases) and 446 patients without DR and with ≥10 years of DM (controls). TheTGFB1rs1800469 and rs1800470 polymorphisms were genotyped by real-time PCR. Frequency of rs1800469 T/T genotype was higher in controls compared to DR cases (18.3%vs. 12.7%, P= 0.022). This genotype remained associated with protection for DR, adjusting for covariables (OR= 0.604; 95% CI 0.395 - 0.923; P= 0.020, recessive model). The rs1800470 C/C genotype was observed in 25.4% of the controls and 18.0% of the cases (P= 0.015); thus, being associated with protection against DR under the recessive model (OR= 0.589; 95% CI 0.405 - 0.857; P= 0.006), adjusting for covariables. In conclusion, theTGFB1rs1800469 and rs1800470 polymorphisms are associated with protection against DR in DM patients from Southern Brazil.