Diabetes impairs wound healing by priming neutrophils to undergo NETosis, a process that releases extracellular traps (NETs) containing cytotoxic proteins and DNA, which can damage tissues. This study shows that neutrophils from both type 1 and type 2 diabetic individuals and mice are more prone to NETosis compared to non-diabetic counterparts. Elevated expression of peptidylarginine deiminase 4 (PAD4), an enzyme involved in chromatin decondensation, is observed in diabetic neutrophils. In diabetic mice, higher levels of citrullinated histone H3 (H3Cit), a marker of NETs, are found in wounds, leading to delayed healing. In contrast, PAD4-deficient mice show accelerated wound healing, suggesting that NETs are a major factor in delayed healing in diabetes. DNase 1, which degrades NETs, also accelerates wound healing in diabetic and normoglycemic mice. NETs, originally recognized as a host defense mechanism, can also cause tissue damage. In diabetes, increased superoxide and cytokine production, along with elevated tumor necrosis factor-α, may promote NETosis. Diabetic neutrophils are more susceptible to NETosis due to higher glucose levels and increased intracellular calcium. This study demonstrates that high glucose concentrations in vitro prime neutrophils to undergo NETosis, and that PAD4 is essential for this process. In mouse models, diabetic mice show increased NET formation and delayed healing, while PAD4-deficient mice heal faster. DNase 1 treatment reduces NETs and accelerates healing in diabetic mice. These findings suggest that inhibiting NETosis or cleaving NETs could improve wound healing and reduce chronic inflammation in diabetes. The study also highlights the role of NETs in inflammatory and thrombotic diseases, and suggests that targeting NETs may offer therapeutic benefits for diabetic wounds and other conditions.Diabetes impairs wound healing by priming neutrophils to undergo NETosis, a process that releases extracellular traps (NETs) containing cytotoxic proteins and DNA, which can damage tissues. This study shows that neutrophils from both type 1 and type 2 diabetic individuals and mice are more prone to NETosis compared to non-diabetic counterparts. Elevated expression of peptidylarginine deiminase 4 (PAD4), an enzyme involved in chromatin decondensation, is observed in diabetic neutrophils. In diabetic mice, higher levels of citrullinated histone H3 (H3Cit), a marker of NETs, are found in wounds, leading to delayed healing. In contrast, PAD4-deficient mice show accelerated wound healing, suggesting that NETs are a major factor in delayed healing in diabetes. DNase 1, which degrades NETs, also accelerates wound healing in diabetic and normoglycemic mice. NETs, originally recognized as a host defense mechanism, can also cause tissue damage. In diabetes, increased superoxide and cytokine production, along with elevated tumor necrosis factor-α, may promote NETosis. Diabetic neutrophils are more susceptible to NETosis due to higher glucose levels and increased intracellular calcium. This study demonstrates that high glucose concentrations in vitro prime neutrophils to undergo NETosis, and that PAD4 is essential for this process. In mouse models, diabetic mice show increased NET formation and delayed healing, while PAD4-deficient mice heal faster. DNase 1 treatment reduces NETs and accelerates healing in diabetic mice. These findings suggest that inhibiting NETosis or cleaving NETs could improve wound healing and reduce chronic inflammation in diabetes. The study also highlights the role of NETs in inflammatory and thrombotic diseases, and suggests that targeting NETs may offer therapeutic benefits for diabetic wounds and other conditions.