During obesity, macrophages infiltrate the visceral adipose tissue and promote inflammation that contributes to type ii diabetes. evidence suggests that the rewiring of cellular metabolism can regulate macrophage function. However, the metabolic programs that characterize adipose tissue macrophages (ATM) in obesity are poorly defined. Here, we demonstrate that ATM from obese mice exhibit metabolic profiles characterized by elevated glycolysis and oxidative phosphorylation, distinct from ATM from lean mice. Increased activation of HIF-1α in AtM of obese visceral adipose tissue resulted in induction of IL-1β and genes in the glycolytic pathway. Using a hypoxia-tracer, we show that HIF-1α nuclear translocation occurred both in hypoxic and non-hypoxic AtM suggesting that both hypoxic and pseudohypoxic stimuli activate HIF-1α and its target genes in AtM during diet-induced obesity. Exposure of macrophages to the saturated fatty acid palmitate increased glycolysis and HIF-1α expression, which culminated in IL-1β induction thereby simulating pseudohypoxia. Using mice with macrophage-specific targeted deletion of HIF-1α, we demonstrate the critical role of HIF-1α-derived from macrophages in regulating ATM accumulation, and local and systemic IL-1β production, but not in modulating systemic metabolic responses. collectively, our data identify enhanced glycolysis and HIF-1α activation as drivers of low-grade inflammation in obesity. Obesity and its associated metabolic diseases, insulin resistance and type 2 diabetes, continue to increase in the United States and worldwide 1 , and fully effective therapies to combat this growing epidemic are lacking. Obesity gives rise to a state of chronic inflammation, which is causally linked to insulin resistance (IR) and type 2 diabetes 2-4. In obese mice and humans, there is a striking accrual of macrophages in visceral adipose tissue 5,6 , and these immune cells are key contributors to obesity-induced insulin resistance 2,7. Whereas adipose tissue macrophages (ATM) comprise approximately 10-15% of stromal cells in the lean adipose tissue, during high fat diet feeding the recruitment of monocytes into visceral adipose depots can drive macrophage accumulation up to 50% of all cells in obese adipose tissue 7. A number of factors, including adipocyte hypertrophy, increased extracellular lipid concentrations and oxidative stress are thought to drive expression of chemoattractant factors that recruit monocytes in the expanding adipose tissue 2,7. In this metabolically disturbed environment, the monocyte-derived macrophages take on an inflammatory phenotype that is distinct from those of macrophages residing in lean adipose tissue 8,9. These ATMs are a source of inflammatory cytokines, particularly TNFα 10 and IL-1β 11 , that sustain the local and systemic inflammation that contributes to insulin resistance [reviewed in 2 ], yet the mechanisms that drive metabolic inflammation and the pro-inflammatory ATM phenotype, remain poorly understood.