Objective To investigate the effects of allopregnanolone(APα) on the dopaminergic neurons in substantia nigra, striatal dopaminergic neural fibers and behavioral performance in Parkinson’s disease (PD) model mice, as well as its possible molecular mechanisms.   Methods  C57BL/6 adult male mice with 20-25 g at 3-month old (n=90) were successively injected with 6-hydroxydopamine (6-OHDA) to generate a PD animal model. APα and its receptor γ-aminobutyric acid A receptor (GABAAR) antagonist—bicuculline (Bic) were successively injected. ELISA was used to detect the APα or dopamine concentration in the serum, cerebral cortex and striatum. The number of tyrosine hydroxylase (TH) in the substantia nigra (SN) and striatal dopaminergic neural projections were examined by immunohistochemical staining. The expression levels of GABAAR in membrane fractions and Ca²⁺/calmodulin-dependent protein kinase Ⅱ δ3 (CaMKⅡδ3), phosphorylated CaMKⅡδ3 (p-CaMKⅡδ3), brain derived neurotrophic factor (BDNF), and cyclin-dependent kinases 1 (CDK1) were detected by Western blotting in the cytoplasmic or nuclear fractions. The interaction of CaMK Ⅱδ3/p-CaMK Ⅱδ3 with BDNF and CDK1 was verified by immunoprecipitation. In addition, the behavioral changes of animals were recorded.   Results There was a significant decrease in the endogenous APα levels of the cerebral cortex, or the dopaminergic neurons of the SN, or the striatal dopaminergic neural fibers, or various protein levels of the membrane, cytoplasmic and nuclear fractions, as well as motor function in PD mice. As compared with PD mice, the abovementioned results were ameliorated in the mice administrated with APα, which were pulled down in mice pre-treated with Bic. The immuno-precipitated result  indicated that CaMKⅡδ3 or p-CaMKⅡδ3 interacted with BDNF or CDK1.   Conclusion  By increasing the endogenous APα levels, exogenous APα treatment can improve SN-striatum dopaminergic neurons in PD model mice by regulating GABAAR/CaMKⅡδ3/BDNF/CDK1 signaling pathway, which in turn promotes behavioral performance in 6-OHDA-lesioned mice.