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Compared with imaging in the visible (400–650 nm) and near‐infrared window I (NIR‐I, 650–900 nm) regions, imaging in near‐infrared window II (NIR‐II, 1000–1700 nm) is a highly promising in vivo imaging modality with improved resolution and deeper tissue penetration. Here, a small molecule NIR‐II dye,5,5′‐(1H,5H‐benzo[1,2‐c:4,5‐c′] bis[1,2,5]thiadiazole)‐4,8‐diyl)bis(N,N‐bis(4‐(3‐((tert‐butyldimethylsilyl)oxy)propyl)phenyl) thiophen‐2‐amine), is successfully encapsulated into phospholipid vesicles to prepare a probe CQS1000. The novel NIR‐II probe is studied for in vivo multifunctional biological imaging. The results of this study indicate that the NIR‐II vesicle CQS1000 can noninvasively and dynamically visualize and monitor many physiological and pathological conditions of circulatory systems, including lymphatic drainage and routing, angiogenesis of tumor, and vascular deformity such as arterial …