Objective To establish a human SNCA whole-bRain transgenic mouse model, and to obtain preliminarily data on the role of α-synuclein in the central nervous system. Methods rAAV2 / 9 (1 × 10¹³ genome copies (GC) / mL) carrying either human SNCA-EGFP or EGFP was bilateral injected intracerebroventricularly in mice at postnatal day 0. The expression pattern and subcellular localization of α-synuclein was examined at 2 weeks and 3 months of age by immunofluorescence and Western blot. Glial profile and pathological changes were analyzed by immunofluorescence and immunohistochemical staining. Results hSNCA transgenic mice were successfully constructed, and α-synuclein was widely expressed throughout the brain, with high expression in the olfactory bulb, cerebral cortex, hippocampus, interbrain and midbrain. Furthermore, nuclear α-synuclein was detected in the olfactory bulb, cerebral cortex, CA2 / 3 of the hippocampus and Purkinje cells of the cerebellum. Overexpression of α-synuclein caused the proliferation of astrocytes and microglia. In addition, pS129 and aggregation of α-synuclein were observed in the olfactory bulb and cerebral cortex. Conclusions hSNCA whole-bRain transgenic mouse model was established successfully, with high long-term expression of α-synuclein and enhanced gliosis and α-synuclein pathology. This model should be useful for studying the physiological function of α-synuclein and its role in Parkinson’s disease.