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Age‐dependent changes in adipose tissue are thought to play a role in development of insulin resistance. A major age‐dependent change in adipose tissue is the downregulation of key proteins involved in carbohydrate metabolism. In the current study, we investigate the role of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase 3 (PFKFB3) a key governor of the rate of glycolysis in adipocytes via the synthesis of fructose‐2,6‐bisphosphate that was significantly downregulated in aged mice. We employed an adipocyte‐specific PFKFB3 mouse line to investigate the role of PFKFB3 on adipocyte function. In both aged mice and PFKFB3‐knockout mice, we observed an increase in O‐glcNAcylated proteins consistent with a shift in glucose metabolism toward the hexosamine biosynthetic pathway. Under chow‐fed conditions, PFKFB3 knockout resulted in significantly smaller adipocyte area, but no difference in total fat mass. While glucose tolerance was unchanged under chow conditions, when mice were challenged with a 4 weeks high‐fat feeding, PFKFB3 deletion led to a greater decrease in glucose tolerance as well as a significant increase in macrophage infiltration. These results indicate that perturbation of the glycolytic pathway in adipose tissue has multiple effects of adipocyte biology and may play a significant role in metabolic changes associated with aging. Results of this student support the notion that changes in glucose metabolism in adipose tissue impact whole‐body metabolism. [ABSTRACT FROM AUTHOR]