Context: Glucose ingestion induced hyperglycemia has been known to induce inflammation, which is related to pathogenesis of diabetic complications. Objective: To examine acute gene expression responses to physiologic oral glucose ingestion in human circulating leukocytes Design: Microarray study of human circulating leukocytes sampled before, 1 hour after and 2 hours after glucose ingestion Participants: Healthy community-based participants (n=60) Main outcome measures: Gene expression changes after glucose ingestion among 48,803 probes Results: Ingestion of 75g glucose successfully induced acute hyperglycemia (glucose concentration 91.6±5.3 mg/dl for fasting and 180.7±48.5 mg/dl for 1 hour after glucose ingestion). Oral glucose ingestion significantly increased expression of 23 genes and decreased expression of 13 genes (FDR p value < 0.05). These genes involved significantly in immunity, natural killer cell mediated immunity, granulocyte-mediated immunity and cytokine mediated signaling pathway (FDR P value <0.05). Conclusions: The present study demonstrated 36 genes which showed acute gene expression change in human leukocytes within 1 hour after glucose ingestion and suggest that leukocytes participate in the inflammatory process induced by acute hyperglycemia. We believe that these results will provide some basic insight into the role of leukocytes in hyperglycemia induced inflammation and pathogenesis of diabetic complication.