Objective Intracranial injection of α-synuclein preformed fibrils (α-syn PFF)in A53T transgenic mice accelerates the onset of Parkinson"s disease pathology, facilitating the rapid establishment of a Parkinson’s disease mouse model. Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group, with isogenic C57 mice as the control group. α-Syn PFF was injected into the bilateral striatum using stereotactic brain injection. After modeling, the open field test was used to assess spontaneous activity and anxiety-like behavior, while the rotarod, grip strength, and pole tests evaluated motor coordination and limb muscle tone. The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and α-syn pathology in the mouse brain. Results Compared to the control group, One month after α-syn PFF injection, model mice showed increased locomotion in the open-field test, with no significant differences in the rotarod, grip strength, or pole tests, but prolonged food-seeking time. By two months, locomotion decreased, motor coordination and muscle tone weakened, and food-seeking time further increased. Phosphorylated α-synuclein levels were elevated in the substantia nigra, cortex, and hippocampus, with microglial activation, Lewy body deposition, and significant dopaminergic neuron loss in the substantia nigra. Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-syn PFF injection. Significant pathological changes were observed, including the aggregation of α-synuclein/LBs in the substantia nigra, cortex, and hippocampus, and the loss of dopaminergic neurons in the substantia nigra. This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson"s disease.