Post-stroke depression (PSD) is a significant and disabling complication affecting approximately one-third of stroke survivors. The pathogenesis of PSD involves neuroinflammation, which is characterized by the activation and functional changes of astrocytes and microglia. These cells play dual roles in PSD by producing pro-inflammatory and anti-inflammatory cytokines, affecting monoamine neurotransmitters, and modulating glutamate levels. Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α exacerbate neuroinflammation and contribute to PSD, while anti-inflammatory cytokines like IL-10 and TGF-β have protective effects. Microglia can polarize into M1 (pro-inflammatory) or M2 (anti-inflammatory) subtypes, with M1 microglia promoting neuroinflammation and M2 microglia offering neuroprotection. Astrocytes also undergo phenotypic changes, with A1 astrocytes contributing to PSD by producing pro-inflammatory cytokines and A2 astrocytes releasing neurotrophic factors like BDNF. The balance between pro-inflammatory and anti-inflammatory factors, as well as the polarization of microglia and astrocytes, is crucial in the development and treatment of PSD. Targeting these cellular processes may provide potential therapeutic strategies for PSD.Post-stroke depression (PSD) is a significant and disabling complication affecting approximately one-third of stroke survivors. The pathogenesis of PSD involves neuroinflammation, which is characterized by the activation and functional changes of astrocytes and microglia. These cells play dual roles in PSD by producing pro-inflammatory and anti-inflammatory cytokines, affecting monoamine neurotransmitters, and modulating glutamate levels. Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α exacerbate neuroinflammation and contribute to PSD, while anti-inflammatory cytokines like IL-10 and TGF-β have protective effects. Microglia can polarize into M1 (pro-inflammatory) or M2 (anti-inflammatory) subtypes, with M1 microglia promoting neuroinflammation and M2 microglia offering neuroprotection. Astrocytes also undergo phenotypic changes, with A1 astrocytes contributing to PSD by producing pro-inflammatory cytokines and A2 astrocytes releasing neurotrophic factors like BDNF. The balance between pro-inflammatory and anti-inflammatory factors, as well as the polarization of microglia and astrocytes, is crucial in the development and treatment of PSD. Targeting these cellular processes may provide potential therapeutic strategies for PSD.