Parkinson’s disease (PD) is characterized by striatal dendritic spine loss and microglial reactivity, but the role of microglia in this process is not well understood. We addressed this question in a mouse model of hemi-parkinsonism induced by unilateral 6-hydroxydopamine intracerebral administration. Medium spiny neurons were sparsely labeled to examine dendritic spine density and morphology, while microglial reactivity was assessed by immunostaining and 3D cell reconstruction at 1-, 2- and 4-weeks post-lesion (n=5 animals/group). Microglia showed a rapid, multiphasic response that evolved over one to four weeks after lesion: an early phase of proliferation and local clustering, followed by transient retraction of processes with reduced coverage and branching complexity, and a later stage with persistent soma enlargement. In parallel, medium spiny neurons progressively lost dendritic spines, coinciding with increased microglial engulfment signals, suggesting active participation of microglia in synaptic remodeling. Together, these results describe a dynamic sequence of structural and functional changes in microglia that overlap with synaptic pruning. They highlight microglia as active player in striatal remodeling and reveal critical time windows that could be targeted to modulate parkinsonism-related plasticity.