Abstract：Macrophages are tissue-resident immune cells that perform diverse functions, ranging from maintenance of tissue homeostasis to first-line host defense against pathogens. Meanwhile, malfunctions of macrophages contribute to pathogenesis of numerous human disease conditions including but not limited to acute and chronic inflammatory diseases, metabolic disorders and tumor. Thus, understanding key events and regulators governing macrophage functionality, especially in the context of tissue microenvironments, would deepen our understanding of basic macrophage biology and aid in designing therapeutic approaches targeting macrophages. Despite of tremendous progresses regarding pathways and molecules regulating macrophage activation and function, how macrophages adapt and respond to specific tissue environments  in vivo in steady state and disease conditions remain surprisingly limited. I will share some examples of our preliminary thoughts on macrophage-tissue interactions although much work needs to be carried out in the future to consolidate various observations into a plausible conceptual framework.