The purpose of this study was to analyse the dynamics of red blood cells (RBC) and white blood cells (WBC) in the retinal capillaries of C57BL/KS db/db mice, a genetic model of type 2 diabetes, and control mice, at different ages. Modified epifluorescence microscopy was used to analyse the capillary velocity of FITC-labeled RBC and rhodamine-labeled WBC in the retina. C57BL/KS db/db diabetic mice were compared to heterozygous non-diabetic mice at ages 8 and 18 weeks (n=6 in each group). At 8 weeks, when hyperglycemia begins in db/db mice, no significant difference was found between average RBC and WBC velocity of the 2 groups. At 18 weeks, RBC velocity was significantly higher in diabetic mice compared to controls (1.21+/-0.29 versus 1.08+/-0.28 mm sec(-1) p=0.0003). No significant difference was found between WBC velocities (0.87+/-0.3 versus 0.85+/-0.3 mm sec(-1)) even when normalized by RBC velocity values. Temporal and spatial coefficients of variation were significantly higher for WBC than RBC velocities (p<0.0001) but were not significantly different in diabetic and control mice. Direct measurement of RBC velocity with this new method showed that it was higher in the retinal capillaries of diabetic than control mice after 10-12 weeks of hyperglycemia, but not at the onset of hyperglycemia. This suggests that enhanced RBC velocity is not an immediate effect of hyperglycemia but a consequence of persistent hyperglycemia. The above results are in line with the hypothesis that microvascular flow increases in diabetes, as one of the first microvascular alterations. In contrast, WBC velocity was not different in diabetic and control mice.