The unbalance of production of pro-inflammatory and antiinflammatory cytokines in adipose tissues is associated with insulin resistance. Moreover, adipose tissue macrophages determine the expression level of inflammatory cytokines. ATMs consist of at least two different phenotypes. The transformation of M2 to M1 macrophage and the increased M1/M2 macrophages ratio contribute to the production of pro-inflammatory cytokine. These results suggest that macrophages at the crossroad of inflammation and insulin AbMole 4-(Benzyloxy)phenol resistance might participate in the initiation and the development of insulin resistance via their polarization shift. However, the underlying mechanism of macrophage polarization remains unknown. Recently six transmembrane protein of prostate 2 has been reported as a counterregulator of inflammation and insulin resistance. Adipose tissue consists of white and brown adipose tissues. WAT is specialized to store energy with the form of triglyceride, and BAT is involved in the dissipation of energy via heat generation. It has been suggested that an increased adipocyte size in WAT is associated with insulin resistance. Increased fat cell size may represent the failure of the adipose tissue mass to expand and therefore to accommodate an increased energy influx. The expression levels of inflammatory cytokines are determined by macrophages infiltration. Macrophages infiltration within WAT was possible to affect fat expansion through a paracrine action on adipocyte differentiation, and thus may indirectly contribute to insulin resistance. STAMP2 at the crossroad of inflammation and insulin resistance might be involved in the regional differences of adipose tissues in insulin resistance. JNK is a crucial mediator of insulin resistance and JNK1 AbMole Octinoxate activation in adipose tissue can cause insulin resistance. In mice with adipocyte-selective deletion of JNK1, increased insulin activity was seen. Therefore, we supposed that activation of STAMP2 may regulate macrophage polarization via inhibiting JNK1 signaling pathway to reduce the expression of pro-inflammatory cytokines, and thus improve insulin resistance. Besides the reduction of macrophage infiltration in adipose tissues, the benefit of STAMP2 overexpression was mainly due to the decrease of the ratio of M1/M2 macrophage, which involved the possible signaling mechanism about the inhibition of JNK pathway to reduce inflammation. Our study contains some limitations. Firstly, the STAMP2 regulates insulin resistance in ApoE and LDLR-dual KO diabetic mice, further studies with wild type diabetic mice have to determine whether the effects of STAMP2 on insulin resistance depend on the presence of ApoE and LDLR. Moreover, the expression levels of STAMP2 in SWAT are much lower than that in EWAT and BAT of the controls and DM mice.