Adipocytes play a critical role in energy storage and endocrine signaling and are associated with various diseases such as cancer and diabetes. Facile strategies to engineer adipocytes have long been pursued for elucidating adipocyte biology and developing adipocyte-based therapies. Herein, we report metabolic glycan labeling of adipocytes and subsequent targeted modulation of adipocytes click chemistry. We show that azido tags expressed on the surface of adipocytes can persist for over 4 days. By conjugating dibenzocyclooctyne (DBCO)-cargos onto azido-labeled adipocytes click chemistry, the cargos can be retained on the adipocyte membrane for over 12 hours. We further show that signaling molecules including adiponectin, calreticulin, mannose-binding lectin 2, and milk fat globule-EGF factor 8 protein can be conjugated to adipocytes to orchestrate their phagocytosis by macrophages. The azido-labeled adipocytes grafted into mice can also mediate targeted conjugation of DBCO-cargos . This adipocyte labeling and targeting technology will facilitate the development of adipocyte-based therapies and provides a new platform for manipulating the interaction between adipocytes and other types of cells.