Aims To estimate the prevalence of diabetic retinopathy (DR) and the possible risk factors associated with DR, in a population of south India. Methods A cross-sectional sample of subjects aged 30 years and older was selected using a cluster sampling technique from Theni district of Tamilnadu state. Eligible subjects were identified through a door-to-door survey and fasting blood glucose estimation. History of diabetes was elicited, and height, weight and blood pressure were measured for all subjects. Ocular examinations including visual acuity and anterior and posterior segment examinations were performed at preselected sites within clusters. Results Among the 25 969 persons screened for diabetes mellitus (DM), 2802 (10.8%) (95% CI 9.3 to 12.2%) were found to have DM. DR was detected in 298 (1.2%) of 25 969 subjects. The age–gender-adjusted prevalence of DR is 0.05% (95% CI 0.04 to 0.06%) for rural and 1.03% (95% CI 0.89 to 1.12%) for urban areas. The overall age–gender-cluster adjusted prevalence of DR was 0.74% (95% CI 0.66 to 0.83%). Diabetic retinopathy was present in 12.2% (95% CI 10.4 to 14.1%) of the DM population. Conclusion Adequate training of ophthalmologists in treating DR and improvement in eye-care infrastructure are needed to tackle this major public health problem in India.