Objective The aim of this study was to develop a transgenic rat model of Parkinson’s disease by lentiviral vector?mediated overexpression of human α?synuclein in the substantia nigra of rats. Methods Lentiviral expression vectors were constructed by inserting the normal α?synuclein gene (WT) or the α?synuclein gene with an A30P mutation (A30P) downstream of the Cytomegalovirus (CMV) promoter (pLKO?CMV?α?SYN?WT?P2A?GFP and pLKO2?CMV?α?SYN?A30P?P2A?GFP). The vectors were transduced into 293FT cells, and α?synuclein protein levels were detected by western blotting after transient transfection for 24 h. Following the packaging, enrichment, the viral suspension with control, and normal or mutated forms of α?synuclein, were stereotaxically injected into the substantia nigra. After 21 days, the rats were euthanized, and the substantia nigra harvested and processed for immunofluorescence to detect α?synuclein and tyrosine hydroxylase (TH) expression, and changes in numbers of neurons. Motor performance was also assessed in the A30P rats using the rotating rod test. Results Each lentiviral vector induced equivalent levels of normal or A30P mutated α?synuclein expression. Compared with the control group, both the wild type and A30P mutant groups showed an obvious reduction in numbers of dopaminergic neurons in the substantia nigra, with significantly greater injury in the A30P group. Immunofluorescence staining experiments in the injured region of A30P mutant rats showed largely absent TH staining, but abundant α?synuclein immunoreactive aggregation. The human α?synuclein group was also associated with a marked reduction in TH expression, indicating that A30P mutant overexpression caused neuronal degeneration. In addition, A30P mutant rats showed a progressive decline in motor performance. Conclusions We have established a human α?synuclein A30P transgenic rat model of Parkinson’ s disease, which may be useful for understanding the pathogenesis and developing treatments for this disorder.