Objective To preliminarily explore the neuroprotective effect of acetate (Ace) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson disease mice and its mechanism. Methods Twenty-four mice were randomly divided into control group, MPTP group and MPTP+Ace group (8 mice in each group). The mice in the control group and MPTP group drank normal drinking water, and those in the MPTP+Ace group drank water containing 1 mol/L Ace. After 7 d, 30 mg/kg MPTP was injected intraperitoneally into the mice in the MPTP group and MPTP+Ace group to induce Parkinson disease model for 7 d. The motor function and cognitive function of mice were detected by tremor paralysis score, pole climbing test and Morris water maze, the activation of microglia in mouse hippocampus was detected by immunohistochemistry, the expression of proinflammatory cytokines in the peripheral blood and hippocampus was detected by enzyme-linked immunosorbent assay (ELISA), and the protein expression of p38 and p65 of nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway in the hippocampus was detected by Western blotting. Results Compared with the control group, the tremor paralysis score of the MPTP group was higher (P<0.05), the pole climbing time was longer (P<0.01), and the percentage of stay time in the target quadrant, the percentage of distance and the times of crossing the platform were decreased (all P<0.01). Compared with the MPTP group, the tremor paralysis score of the MPTP+ace group was lower (P<0.05), the pole climbing time was shorter (P<0.01), and the percentage of stay time in the target quadrant, the percentage of distance and the times of crossing the platform were increased (all P<0.01). Compared with the control group, the activated microglia in hippocampus of mice in the MPTP group were increased, the expression levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the serum and hippocampus were increased (all P<0.01), and the expression levels of phosphorylated p38 and phosphorylated p65 proteins in the hippocampus were increased (both P<0.01). Compared with the MPTP group, the activated microglia in the hippocampus of mice in the MPTP+Ace group were decreased, the expression levels of TNF-α and IL-6 in the serum and hippocampus were decreased (all P<0.05), and the expression levels of phosphorylated p38 and phosphorylated p65 in hippocampus were decreased (both P<0.01). Conclusion Ace can reduce microglia activation in the hippocampus by inhibiting NF-κB/MAPK inflammatory signaling pathway, inhibit the inflammatory response of central nervous system, and improve motor function and cognitive function of MPTP-induced Parkinson disease mice.