Recent experimental data suggest that a microsatellite polymorphism at 5' end of the aldose reductase gene may be associated with the development of diabetic retinopathy. In the present study, we examined the allele distribution of the polymorphism in 384 Hong Kong Chinese patients who had late-onset (age at diagnosis > or =35 years) Type 2 diabetes, but no clinical evidence of cataract. Approximately 17% of them (n = 64) had retinopathy. The patients with retinopathy were older (52 +/- 11 years vs. 60 +/- 9 years, p < 0.01) and had a higher HbA1c (8.9 +/- 2.2% vs. 7.7 +/- 2.0%, p < 0.01 with adjustment for age) than those without the complication. Amongst all of the patients, we detected 10 microsatellite alleles and found that allele Z-4 was overpresented in those with retinopathy (9% vs. 4%, p < 0.05). There were no significant differences in allelic distributions of the major alleles Z + 2, Z, and Z-2, which accounted for more than 80% of the overall frequency, between the two groups of patients. Using multiple logistic regression analysis (R2 = 0.17, p < 0.01), we found that age (p < 0.01) and HbA1c (p < 0.05) were associated with retinopathy. In conclusion, our data suggest that the occurrence of diabetic retinopathy in the Chinese population may be influenced by clinical and metabolic factors. The aldose reductase gene may be implicated, but is not likely to play a major role.