This study was performed to clarify the presence of sodium-dependent glucose uptake and its role in the synthesis of type IV and type VI collagen by cultured bovine retinal pericytes. The glucose uptake by retinal pericytes and retinal endothelial cells was measured using 3H-D-glucose in the presence or absence of sodium. Glucose uptake in the presence of sodium was twice as high as that observed in the presence of phlorizin and sodium or in the absence of sodium. Sodium-dependent glucose uptake was observed at different sodium concentrations, and its half-maximal stimulation occurred at 48 mM. These findings were not observed in retinal endothelial cells. Levels of type IV and type VI collagen produced by retinal pericytes were significantly increased at glucose concentrations higher than 20 mM. Phlorizin decreased both collagen synthesis and glucose consumption by retinal pericytes incubated with 30 mM of glucose to the levels observed with 5 mM of glucose. These data suggest that sodium-dependent glucose uptake is present in retinal pericytes and that excessive glucose entry into the cell is an important factor for overproduction of collagen. Phlorizin normalized the synthesis of type IV and type VI collagen with decreasing glucose consumption under high glucose conditions.