AIM: To observe the intervention effect of Chinese medicine Kangzhen Zhijing spasmodic decoction Ⅰ on the progression of Parkinson's disease in mice, and to explore the potential mechanism of neuroprotection. METHODS: Thirty-six C57BL/6 mice were randomly divided into control group, model group, drug group and positive drug group. In the model group, the drug administration group and the positive drug group,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg) was injected intraperitoneally for 5 days to establish the mouse model. The control group was given the same amount of normal saline，the drug administration group was given 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg dose of Chinese medicine Kangzhen Zhijing spasmodic Decoction Ⅰ by gavage, and the positive drug group was given 75 mg/kg Madopar by gavage. Behavioral tests were performed on the second day after the administration in each group. Immunopositive cells of Tyrosine hydroxylase (TH),Amyloid precursor protein (APP), α-synuclein (α-syn) and solute carrier family 6 member 11 (SLC6A11) were detected by immunohistochemistry. The protein expressions of TH, APP, α-syn and SLC6A11 in each group were detected by Western blot. RESULTS: It could significantly improve the weight loss of mice in the model group, alleviate the decline of autonomic activity in open field test and the decline of coordination ability in pole test and suspension test. In the reverse immunohistochemistry and Western Blot experiments, the expressions of TH and SLC6A11 in the brain of the Parkinson's model group were significantly decreased, and the expressions of APP and α-syn were significantly increased. CONCLUSION: Kangzhen Zhijing spasmodic decoction Ⅰ can significantly improve the behavioral performance of Parkinson's disease mice and effectively improve the reduction of neuronal transmitters.