Chronic low-grade inflammation, particularly in the adipose tissue, orchestrates obesity-induced insulin resistance. In this process, polarized activation of macrophages plays a crucial role. However, how macrophages contribute to insulin resistance remains obscure. Class A scavenger receptor (SR-A) is a pattern recognition receptor primarily expressed in macrophages. Through a combination of in vivo and in vitro studies, we report here that deletion of SR-A resulted in reduced insulin sensitivity in obese mice. The anti-inflammatory virtue of SR-A was accomplished by favoring M2 macrophage polarization in adipose tissue. Moreover, we demonstrate that lysophosphatidylcholine (LPC) served as an obesity-related endogenous ligand for SR-A promoting M2 macrophage polarization by activation of signal transducer and activator of transcription 6 signaling. These data have unraveled a clear mechanistic link between insulin resistance and inflammation mediated by the LPC/SR-A pathway in macrophages.