AbstractPulmonary inflammation is one of the most reported tissue inflammations in clinic. Successful suppression of inflammation is vital to prevent further inevitably fatal lung degeneration. Glucocorticoid hormone, such as methylprednisolone (MP), is the most applied strategy to control the inflammatory progression yet faces the challenge of systemic side effects caused by the requirement of large‐dosage and frequent administration. Highly efficient delivery of MP specifically targeted to inflammatory lung sites may overcome this challenge. Therefore, the present study develops an inflammation‐targeted biomimetic nanovehicle, which hybridizes the cell membrane of mesenchymal stem cell with liposome, named as MSCsome. This hybrid nanovehicle shows the ability of high targeting specificity toward inflamed lung cells, due to both the good lung endothelium penetration and the high uptake by inflamed lung cells. Consequently, a single‐dose administration of this MP‐loaded hybrid nanovehicle achieves a prominent treatment of lipopolysaccharide‐induced lung inflammation, and negligible treatment‐induced side effects are observed. The present study provides a powerful inflammation‐targeted nanovehicle using biomimetic strategy to solve the current challenges of targeted inflammation intervention.