There is a growing debate in the literature on whether glucose variability contributes, as well as high HbA1c levels and longstanding diabetes, to the onset and progression of diabetic retinopathy (DR) in patients with diabetes types 1 (DM1) and 2 (DM2). Few data, obtained only by self-monitoring of blood glucose, support this hypothesis. We used continuous glucose monitoring (CGM) to investigate the association between DR and glucose variability parameters (SD, CONGA 2, MAGE), acute hyperglycemia (HBGI) and chronic exposure to glucose (AG and AUC tot). We studied 68 patients from 19 to 69 years old, 35 with DM1 and 33 with DM2. The prevalence of retinopathy was 43 % in DM 1 patients and 39 % in DM 2 patients. The values of all indicators were obtained by CGM for 72 h. DR was diagnosed on direct or indirect ophthalmoscopic examination, after inducing mydriasis with tropicamide. HbA1c was measured at the baseline and 6 weeks after CGM to test the stability of the patients' glycemic control. Univariate analysis showed a close association between DR and duration of diabetes (OR 1.11; 1.04-1.19), intensive insulin therapy (OR 5.6, CI 1.14-27.30), SD (OR 1.03; CI 1.01-1.06) and CONGA 2 (OR 1.02; CI 1.00-1.04)-both indicators of variability and HBGI (OR 1.1, CI 1.01-1.18)-a parameter reflecting acute hyperglycemia. There was no significant correlation with HbA1c (p = 0.070). Multivariate regression analysis showed that disease duration is the parameter most significantly correlating with DR (OR 1.05; 1.01-1.15). These results reinforce the evidence that longstanding disease is the factor most closely associated with DR. Our data also suggest, however, that glucose variability-regardless of HbA1c-may also have a role as a risk factor for DR, particularly in the case of acute fluctuations (as represented by CONGA 2 and SD) and acute hyperglycemia (as represented by HBGI).