Paw edema is a classic acute inflammation model, which is often used in clinical screening and evaluation of anti-inflammatory effects of drugs. As an endogenous gas signaling molecule, hydrogen sulfide (H2S) is closely related to the progression of paw edema inflammation. However, no fluorescent probes have been reported to visualize H2S levels in paw edema mice. Herein, a novel near-infrared (NIR) fluorescent probe (BAX-N) is developed to detect H2S. The NIR dye formed by the conjugation of benzothiazole-2-acetonitrile with xanthene serves as the fluorophore (BAX-OH), and nitrobenzoxadiazole (NBD) serves as the H2S-responsive group. The fluorescence of BAX-N is quenched due to the photo-induced electron transfer (PET) effect. After the reaction of BAX-N with H2S, the PET effect is blocked and obvious fluorescence appears at 722 nm, while exhibiting large Stokes shift, fast response time, high sensitivity and selectivity. Meanwhile, the possible reaction mechanism of BAX-N toward H2S was proposed and proved by mass spectra (MS), high-performance liquid chromatography (HPLC) and Density functional theory (DFT) calculation. Furthermore, based on the high biosafety of BAX-N, it has been used to monitor fluctuation in H2S levels in cells during inflammatory events. More importantly, BAX-N has been first used for specifically image H2S in paw edema mice and its treatment due to its NIR properties, which will provide a reliable platform for the monitoring of inflammatory conditions and the evaluation of anti-inflammatory drug efficacy.