A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.