White adipose tissue is loose connective tissue having heterogenous nature in composition of cellular components as it contains preadipocytes, adipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells. Immune cells, particularly involved in innate immunity in adipose tissue play the important role in local and systemic metabolism. It has become well established that excessive obesity in mice and humans is associated with a state of chronic low-grade inflammation in adipose tissue characterized with dysregulated innate immune cells. The obesity related chronic inflammation is collectively regulated by a variety of immune cells including macrophages, Innate lymphoid cells (ILC2), T cells, natural killer cells, and eosinophils. In fact, recent studies have found that eosinophils that is upregulated by ILC2 promote alternative activation macrophage polarization by secreting Th2 type cytokines such as IL-13 and IL-4, consequently leading to reduced inflammation in adipose tissue, and meanwhile resulting in increased energy expenditure through nonshivering thermogenesis. These studies provide strong evidence demonstrating Th2 type cytokines, e.g., IL-13 and IL-4 play an unexpected role in regulating immunometabolic homeostasis in adipose tissue. Adipose tissue macrophages (ATMs) are the most abundant immune cell in human and murine adipose tissue (Weisberg et al., 2003). ATMs show significant functional heterogeneity and actively participate in nutrient metabolism within adipose tissue under physiological conditions. Interest in the role of macrophages in shifting adipose tissue inflammation toward a pathologic state is growing. In this context, studies suggest that the STAT6 transcription factor, which is activated upon stimulation by the Th2 cytokines IL-4 and IL-13, promotes maturation of alternatively activated macrophages (Gordon, 2003; Vats et al., 2006). Recent studies show that STAT6 and its associated transcription factors play a critical role in M2-like macrophages by increasing oxidative metabolism and mitochondrial biogenesis (Kang et al., 2008; Odegaard and Chawla, 2011; Odegaard et al., 2007). Blocking oxidative metabolism not only impairs development of an M2-like phenotype, but also drives such cells toward an M1-like state (Rodriguez-Prados et al., 2010). A recent finding shows that Irf5-deficient M2-like macrophages promote insulin sensitivity by secreting TGF-b1 (Dalmas et al., 2015). Furthermore, the failure of alternative M2 activation, which is associated with reduced oxidative function, leads to classical macrophage activation, increased weight gain, and obesity with concurrent adipose inflammation and insulin resistance (Odegaard et al., 2008). These observations indicate that a treatment modality that pushes pro-inflammatory M1-like macrophages toward an anti-inflammatory M2-like phenotype may be beneficial for those with obesity-related insulin resistance. Here, we would like to discuss the identified a secretory factor which is required for increased oxidative metabolism in M2-like macrophages stimulated with IL-4 and the PPAR agonist, rosiglitazone (RSG). Administration of those soluble factor to obese rodents improved the oxidative function of macrophages and reversed insulin resistance. Collectively, these findings identify souble factor as a macrophageregulating paracrine signaling factor that is controlled by STAT6 and PPAR and is required for anti-inflammatory responses in white adipose tissue (WAT).