Introduction: Parkinson's disease (PD) is caused by dopamine (DA)-containing neuron degeneration in the substantia nigra pars compacta (SNpc). Although the brain's neuroinflammatory response has long been thought to play a role in the etiology of this neurological illness, the mechanism remains unknown. Idebenone, which has antioxidant and anti-inflammatory effects and may be beneficial for PD neuroprotection. Approach: PD is a progressive disease, and this is due to the continuous destruction of the nerves that secrete dopamine due to several factors, including inflammation of the dopaminergic neurons. Since patients have a decreased response to PD medications, research is being conducted to find drugs or interventions that halt or reduce the disease's progression while protect the dopaminergic neurons. Idebenone has been shown to have antioxidant and anti-inflammatory actions on neurons. Rationale: PD is a progressive neurodegenerative disorder. It is second most common neurodegenerative disorder that affects 2-3% of the population 65 years of age, and is more common as people age. We suggest investigating the effect of the Idebenone on the model of PD. Aim: This study aimed to investigate the effects of Idebenone in prevention of inflammatory mediators release and protection of dopaminergic neurons from LPS- induced neurotoxicity in rats. Method: Male Wistar rats were administrated oral Idebenone (100 mg/kg/day) for 14 days began on the same day as an intranigral injection of LPS (2 ?g/2 ?l). The LPS- induced lesions were evaluated behaviorally using the Apomorphine rotational test, and neurochemically by detecting dopamine amounts in the striatum, tumor necrosis factor alpha (TNF-?), and brain-derived neurotrophic factor (BDNF) using an enzyme-linked immunosorbent assay (ELISA) kit. Results: Treatment with Idebenone (100 mg/kg/day) on the same day for the LPS- lesioned group significantly decreased TNF-? compared to the group treated with LPS alone. Moreover, it significantly lowered tight contralateral rotations upon Apomorphine challenge, and it increased DA levels slightly compared to the group treated with LPS alone. As well, it slightly reduced the amount of BDNF in comparison to the group treated with LPS alone. Conclusion: Idebenone exerts a neuroprotective effect, improves the neurological impairments associated with PD, and appears to reduce neuroinflammation.