Abstract: OBJECTIVE To study the effect and possible mechanism of idebenone on behavior improvement of Parkinson's disease(PD) mice induced by MPTP. METHODS The mice were divided into control group, model group, high and low dose of idebenone groups. The mice were injected with 20 mg·kg^-1 MPTP for one week to induce Parkinson's disease expect those in control group. The mice in low dose of idebenone group were given idebenone 5 mg·kg^-1 daily while high dose of idebenone group with 10 mg·kg^-1 daily for 14 d. The model group was given saline of equal volume and control group were normally reared. The behavioral tests of mice were performed by open field test, rod climbing test, runner test, swimming test and suspension test. The expression of tyrosine hydroxylase(TH) in substantia nigra of mice was detected by immunohistochemistry, the protein synthesis ability of mice was detected by Nissl staining, the oxidative damage of substantia nigra was detected by MDA and SOD kits, and the apoptosis of substantia nigra neurons was detected by TUNEL staining. Immunohistochemistry detected the expression of IBA-1 in microglia while Western blot detected the expression of Bax, Bcl-2 and caspase-9 in the substantia nigra. RT-qPCR was used to detect mt-ND1 and mRNA expression levels of key transcription factors POLG1, POLG2 and TFAM. The expression of IL-1β, TNF-α, and IL-6 in the peripheral blood of mice was detected by ELISA. RESULTS The movement ability of mice in model group was significantly lower than that of control group, the balance was seriously affected. After the intervention of idebenone, the behavior of mice was significantly improved, which was significantly different from that of model group(P<0.05). Compared with the control group, the expression of TH and SOD in substantia nigra of the model group was significantly down-regulated(P<0.05), the apoptosis rate of neurons and the levels of MDA and IBA-1 were significantly up-regulated(P<0.05), the expression levels of inflammatory factors IL-1β, TNF-α, IL-6 in peripheral blood were significantly up-regulated(P<0.05), the expression of Bax and caspase-9 were up-regulated, the DNA copy number and the related transcription factors were significantly down-regulated(P<0.05). Compared with model group, idebenone could increase the expression of TH and SOD, down-regulate the apoptosis rate, expression of IBA-1 in substantia nigra and inflammatory factors in peripheral blood, and down-regulate the apoptosis related proteins Bax and caspase-9, up-regulate the expression of Bcl-2. Idebenone could also increase the copy number of DNA and expression of related transcription factors. CONCLUSION Idebenone can improve the behavior of Parkinson's disease mice, and its mechanism is related to anti-oxidative stress injury, inhibiting mitochondrial apoptosis signal and improving mitochondrial damage.