Obesity induces a phenotypic switch in adipose tissue macrophage (ATM) polarization. In lean mice, ATMs express genes characteristic of M2 or alternatively activated macrophages, including Ym1, arginase 1, and Il10. However, diet-induced obesity decreases these genes and increases genes associated with M1 or classically activated macrophages, such as TNF-α and iNOS. ATMs from obese Ccr2-KO mice retain M2 markers similar to those in lean mice, suggesting that factors independent of the MCP-1/CCR2 axis influence macrophage recruitment. Obesity leads to a shift in ATM activation from an M2-polarized state to an M1 proinflammatory state, contributing to insulin resistance. ATMs from obese mice express inflammatory genes more than those from lean mice, and IL-10, which is overexpressed in lean ATMs, protects adipocytes from TNF-α-induced insulin resistance. These findings suggest that obesity alters ATM polarization, leading to increased inflammation and insulin resistance. The study highlights the importance of ATM polarization in obesity and insulin resistance, and the potential for targeting ATM polarization to improve insulin sensitivity.Obesity induces a phenotypic switch in adipose tissue macrophage (ATM) polarization. In lean mice, ATMs express genes characteristic of M2 or alternatively activated macrophages, including Ym1, arginase 1, and Il10. However, diet-induced obesity decreases these genes and increases genes associated with M1 or classically activated macrophages, such as TNF-α and iNOS. ATMs from obese Ccr2-KO mice retain M2 markers similar to those in lean mice, suggesting that factors independent of the MCP-1/CCR2 axis influence macrophage recruitment. Obesity leads to a shift in ATM activation from an M2-polarized state to an M1 proinflammatory state, contributing to insulin resistance. ATMs from obese mice express inflammatory genes more than those from lean mice, and IL-10, which is overexpressed in lean ATMs, protects adipocytes from TNF-α-induced insulin resistance. These findings suggest that obesity alters ATM polarization, leading to increased inflammation and insulin resistance. The study highlights the importance of ATM polarization in obesity and insulin resistance, and the potential for targeting ATM polarization to improve insulin sensitivity.