Currently, the exact etiology of Parkinson's disease (PD) has not been fully elucidated and no curative treatment. The aberrant brain metabolism and air pollution exposure of sulfur dioxide (SO2) was closely associated with neurotoxicity. However, the elaborate role of SO2 in PD brain is still undefined due to the lack of a blood-brain barrier (BBB)-permeable molecular tool. Herein, we developed two BBB-penetrable and SO2-responsive near-infrared fluorogenic sensors, PD-SO2-1 and PD-SO2-2 for uncovering the fluctuation of SO2 in PD brain. In vitro results suggested their excellent optical properties towards SO2. Moreover, PD-SO2-2, the o-methoxy modification, displayed a higher signal-to-noise ratio and BBB transport efficiency. In addition, imaging results suggested an incremental SO2 levels in both PD model cells and mice. Importantly, it was revealed that the overexpressed of NADPH oxidase (NOX) participated in the oxidation of hydrogen sulfide (H2S) to SO2 and sulfite oxidase (SOX) was facilitated SO2 metabolism in PD pathological cells. Furthermore, Vitamin B2 (VB2) can alleviate dopaminergic neuron damage both in PD model mice and mice exposed to SO2 air pollution, highlighting the vital interplay between SO2 and PD pathology. Overall, this work provides a robust imaging sensor (PD-SO2-2) for examining the fluctuation of SO2 in PD and unveiled the influence of SO2 air pollution on the pathogenesis of PD, which offered a novel understanding into the PD pathophysiology and therapy.