--- - |2+ Parkinson's disease (PD) is a common neurodegenerative disorder due to the loss of dopaminergic neurons in the substantia nigra. This study focuses on the effect of microRNA‐329 (miR‐329) on nigral dopaminergic neurons in a rat model of PD via the FoxO3a signaling pathway by binding to CDKN2D. Brain tissues from the substantia nigra were taken from the rats in two groups. TUNEL staining was used to observe tyrosine hydroxylase (TH)‐positive neurons. Nigral dopaminergic neurons were randomized into the normal, blank, negative control (NC), miR‐329 mimics, miR‐329 inhibitors, small interfering (siRNA)‐CDKN2D, and miR‐329 inhibitors + siRNA‐CDKN2D groups. Expressions of miR‐329, CDKN2D, FoxO3a, AKT, caspase‐3 and Bcl‐2 were determined using RT‐qPCR and western blotting. Apoptosis rate of nigral dopaminergic neurons in 7 groups was determined by flow cytometry. Compared with the blank and NC groups, the miR‐329 mimics group showed increased miR‐329 and caspase‐3 expressions as well as decreased expressions of CDKN2D, FoxO3a, AKT, and Bcl‐2, the siRNA‐CDKN2D group indicated enhanced expressions of caspase‐3 and declined expressions of CDKN2D, FoxO3a, AKT, and Bcl‐2, and the miR‐329 inhibitors group revealed decreased miR‐329 and caspase‐3 expressions and increased expressions of CDKN2D, FoxO3a, AKT, and Bcl‐2. The apoptosis rate of nigral dopaminergic neurons was significantly increased in the miR‐329 mimics and siRNA‐CDKN2D groups, but was decreased in the miR‐329 inhibitors group. Our data suggested that downregulated miR‐329 could inhibit apoptosis of nigral dopaminergic neurons in a rat model of PD by upregulating the expression of CDKN2D via the activation of the FoxO3a signaling pathway. - Journal of Cellular Physiology, Volume 233, Issue 11, Page 8617-8629, November 2018.