The authors previously reported that blood speeds in the retinal arteries were significantly lower in patients with type I diabetes than in controls without diabetes. The purpose of this long-term, follow-up study was to characterize the natural course of changes in blood speed and blood flow in these patients. Twenty-four patients were followed up with serial annual measurements of the blood flow in a temporal retinal artery using the bidirectional laser Doppler technique and monochromatic photography. The follow-up period ranged from 2 to 6 years (mean, 3.8 years). Using standardized color fundus photography and fluorescein angiography, a retinopathy score was generated for each eye studied. Linear regression analysis was used to compute the slope of the change in retinal blood flow for each patient during the follow-up period. Retinal blood flow slopes were negative in 15 patients and positive in 9 patients. Multiple linear regression analysis showed that the retinal blood flow slopes were significantly related to the retinal blood flow measured at entry to the study and to the median duration of diabetes during the follow-up period (R2= 0.56; P= 0.0002). There was a positive correlation between the retinal blood flow slopes and the median retinopathy score during the follow-up period (P= 0.47; P= 0.02). As duration of diabetes becomes longer and retinopathy becomes more severe, there is a transition from negative to positive retinal blood flow slopes. This bimodal relationship between the change in retinal blood flow and the duration of diabetes reflects the complex pathologic alterations that occur in the diabetic retina.