In diabetes, hyperglycemia is associated with activation of the polyol pathway, in which fructose is endogenously overproduced. When fructose is metabolized in hepatocytes and tubular epithelial cells, ATP depletion and purine nucleotide turnover occur rapidly and irreversibly, and uric acid is eventually generated. The metabolism of fructose to uric acid is also known as the fructose-uric acid axis. Uric acid derived from endogenous fructose could directly impair renal tubular epithelial cells and peritubular capillary endothelial cells, resulting in diabetic tubulopathy. In the course of diabetic nephropathy, tubular injury may be induced earlier than glomerular injury and may be more closely associated with renal function. For this reason, the fructose-uric acid axis as a novel mechanism for the development of diabetic tubular injury provides new insights into the pathogenesis and treatment of diabetic nephropathy.