Objective To investigate the effect of all-trans retinoic acid (ATRA) on dopaminergic neurons in mice with Parkinson's disease (PD) and related mechanisms.Methods Wild-type mice were randomly divided into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT) control group and ATRA+MPTP group. The behavioral test was performed before and after modeling. Flow cytometry was used to measure peripheral T lymphocyte subsets, real-time quantitative PCR was performed to measure the expression of adhesion molecules in the choroid plexus and inflammatory factors in the substantia nigra, and immunofluorescence assay was used to evaluate the activation of glial cells and the survival of dopaminergic neurons in the substantia nigra.Results The PD mice pretreated with ATRA had a significant increase in the number of peripheral regulatory T cells (2.3%±0.21%, P<0.05). There was a significant increase in the expression of PD1, with 4.65%±0.61% in CD4+ regulatory T cells and 3.50%±0.31% in CD8+ regulatory T cells (P<0.05). There were significant reductions in the relative expression of adhesion molecules Icam-1 (0.37±0.13) and Vcam-1 (0.32±0.06) and inflammatory factors interleukin-6 (0.16±0.05) and tumor necrosis factor-α (0.29±0.12) (P<0.05). In the substantia nigra, the activation of glial cells was reduced, and the viability of dopaminergic neurons was increased. There were significant improvements in coordinate ability (total time spent on the rotating rod:157.5±24.5 s) and autonomic activity (total movement distance:42.58±2.96 m) in mice.Conclusions ATRA exerts a protective effect on dopaminergic neurons by enhancing the anti-inflammatory effect of regulatory T cells.