Protocatechuic acid (PCA) at 2 or 4% was supplied to diabetic mice for 12 weeks. PCA treatments increased its deposit in organs and significantly reduced the plasma HbA1c level, the urinary glycative albumin level, and renal production of carboxymethyllysine (CML), pentosidine, sorbitol, and fructose (p < 0.05). However, PCA treatments only at 4% significantly decreased brain content of CML, pentosidine, fructose, and sorbitol (p < 0.05). PCA treatments at 2 and 4% significantly lowered renal activity and mRNA expression of aldose reductase and sorbitol dehydrogenase (p < 0.05), and PCA treatments only at 4% significantly enhanced renal glyoxalase I mRNA expression (p < 0.05). PCA treatments also dose-dependently decreased the renal level of type-IV collagen, fibronectin, and transforming growth factor-β1 (p < 0.05), as well as dose-dependently diminished renal protein kinase C (PKC) activity (p < 0.05); however, PCA treatments only at 4% suppressed renal mRNA expression of PKC-α and PKC-beta (p < 0.05). PCA treatments at 4% significantly restored renal mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ, as well as suppressed expression of the advanced glycation end-product receptor (p < 0.05). These findings suggest that the supplement of PCA might be helpful for the prevention or alleviation of glycation-associated diabetic complications.