Content of protocatechuic acid (PA) in eight locally available fresh fruits was analyzed, and the protective effects of this compound in diabetic mice were examined. PA at 1%, 2%, and 4% was supplied to diabetic mice for 8 weeks. PA treatments significantly lowered plasma glucose and increased insulin levels. PA treatments at 2% and 4% significantly lowered plasminogen activator inhibitor-1 activity and fibrinogen level; increased plasma activity of antithrombin-III and protein C; decreased triglyceride content in plasma, heart, and liver; elevated glutathione level and the retention of glutathione peroxidase and catalase activities in heart and kidney. PA treatments at 2% and 4% also significantly lowered plasma C-reactive protein and von Willebrand factor levels and reduced interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 levels in heart and kidney. These results support that protocatechuic acid could attenuate diabetic complications via its triglyceride-lowering, anticoagulatory, antioxidative, and antiinflammatory effects.