Neutrophils play an active role in acute and chronic inflammation by exhibiting functional heterogeneity. Besides beneficial role in acute infections to eliminate pathogens, neutrophils also contribute to pathogenesis of diseases associated with sterile inflammation including vascular disorders, autoimmune diseases, Type 2 diabetes (T2D) and cancers. During T2D, hyperglycemia constitutively activate neutrophils. In the context of T2D associated complications, we examined influence of high glucose, homocysteine and LPS representing effector molecules of hyperglycemia, thrombosis, and infection respectively on human neutrophil activation to identify distinct signaling pathways by quantitative phosphoproteomics approach.