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Visualizing the progression of fatty liver disease in vivo is of great significance in biomedical research of fatty liver, but hindered by the lack of suitable approaches with deep penetration, high specificity, and real‐time observability for fatty liver imaging. Herein, two bright NIR‐I/NIR‐II fluorophores with D–π–A–π–D structures are designed and synthesized for fatty liver tracking in vivo. Such fluorophores show an ultrahigh quantum yield of 49.2% and 17.3% at the emission maximum of 930 and 975 nm, respectively. Most interestingly, these two fluorophores display ultrasensitive fluorescence response (over 100‐fold enhancement) toward the variations of environment polarity. Accordingly, further doping of these fluorophores into amphiphilic organic matrix allows the formation of ultrabright NIR‐I/NIR‐II fluorescent nanoprobes for high‐resolution fluorescence imaging of the vessels. Additionally, with the assistance of such nanoprobes and NIR‐II fluorescence imaging, real‐time monitoring of heartbeat rate and the respiratory rate, accurate identification, and imaging‐guided surgery of the submillimeter scale lymph nodes are successfully realized. Moreover, the as‐designed fluorophores show superior performance for indicating lipid droplets (LDs) in living cells. Ultimately, precise monitoring of fatty liver with NIR‐I/NIR‐II fluorescent LDs probe is first confirmed, demonstrating the possibility for staging fatty liver disease with a contact‐free method. [ABSTRACT FROM AUTHOR]