Abstract:[Objective] To investigate the effect of streptomycin sulfate on the symptoms and gut microbiota of chronic Parkinson's disease mice. [Methods] Forty C57BL/6 mice were randomly divided into the control group, streptomycin sulfate control group, Parkinson's disease (PD) model group and streptomycin sulfate treated PD model group. PD mice were induced by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) combined with probenecid (250 mg/kg) at the first 5 weeks of the experiment; the streptomycin sulfate treated PD mice began to drink the streptomycin aqueous solution (500 μg/mL) on the first day of the experiment until the end of the experiment. A variety of experimental methods, such as rotarod test, pole test, immunohistochemistry, real-time PCR, and high-throughput sequencing were used to detect the related symptoms and indicators of each group. [Results] Compared with the control, chronic PD mice showed motor impairment (P<0.01), dopaminergic neurons in the nigrostria and their fibers in the striatum reduced significantly (P<0.01), intestinal dysfunction and inflammation, along with the structure of gut microbiota changed significantly:the ratio of Firmicutes/Bacteroides and the abundance of Family Ruminococcaceae increased (P<0.01), whereas the abundance of Family Prevotellaceae and Genus Prevotellaceae_UCG-001 decreased (P<0.01). The intervention of streptomycin sulfate significantly improved the exercise capacity of chronic PD mice (P<0.05), relieved the decrease of dopaminergic neurons and fibers in the nigrostriatal system (P<0.05), and improved the intestinal dysfunction and inflammation, meanwhile reduced the ratio of the Firmicutes/Bacteroides and the abundance of Family Ruminococcaceae, Rikenellaceae and Lactobacillaceae and increased the abundance of Family Prevotellaceae and Genus Prevotellaceae_UCG-001.[Conclusion] Streptomycin sulfate can relieve the symptoms associated with PD mice and affect the gut microbiota of PD mice.