It has been reported that the levels of erythropoietin are associated with diabetes mellitus. Glomerular epithelial cells, located in the renal cortex, play an important role in the regulation of kidney function and hyperglycemia-induced cell loss of glomerular epithelial cells is implicated in the onset of diabetic nephropathy. This study investigated the effect of high glucose on erythropoietin and erythropoietin receptor expression in rat glomerular epithelial cells. We found that 25 mM D-glucose, but not mannitol or L-glucose, stimulated erythropoietin mRNA and protein expression in a time dependent manner (>4 h) in rat glomerular epithelial cells. In addition, 25 mM glucose, but not mannitol or L-glucose, also increased the phosphorylation of erythropoietin receptor, suggesting a role for erythropoietin receptor phosphorylation in erythropoietin synthesis. We conclude that high glucose stimulates erythropoietin production and erythropoietin receptor phosphorylation in rat glomerular epithelial cells.