Microglia, the resident immune cells in the brain, are implicated in the pathology of neurodegenerative diseases. Activated microglia produce multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), leading to progressive neuron damage. Microglial activation can be triggered by a single or multiple stimuli, resulting in cumulative neuronal loss over time. Reactive microgliosis, a chronic response to neuronal damage, and ROS are key mechanisms driving chronic and neurotoxic microglial activation, particularly in Parkinson's disease (PD). The article reviews the mechanisms of neurotoxicity associated with chronic microglial activation and discusses the role of neuronal death and microglial ROS in driving the chronic and toxic microglial phenotype. Key words: Microglia, inflammation-mediated neurodegeneration, oxidative stress, chronic neurotoxicity, reactive microgliosis.Microglia, the resident immune cells in the brain, are implicated in the pathology of neurodegenerative diseases. Activated microglia produce multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), leading to progressive neuron damage. Microglial activation can be triggered by a single or multiple stimuli, resulting in cumulative neuronal loss over time. Reactive microgliosis, a chronic response to neuronal damage, and ROS are key mechanisms driving chronic and neurotoxic microglial activation, particularly in Parkinson's disease (PD). The article reviews the mechanisms of neurotoxicity associated with chronic microglial activation and discusses the role of neuronal death and microglial ROS in driving the chronic and toxic microglial phenotype. Key words: Microglia, inflammation-mediated neurodegeneration, oxidative stress, chronic neurotoxicity, reactive microgliosis.