This study investigates the effects of lactobacillus-derived extracellular vesicles (Lac-EVs) on lipopolysaccharide (LPS)-induced microglial cell activation and inflammation in an in vitro neuroinflammation model. The research aims to explore whether Lac-EVs can modulate microglial polarization and reduce neuroinflammation, particularly by promoting the differentiation of M2 microglia and inhibiting proinflammatory cytokine production. The study found that Lac-EVs reduced LPS-induced inflammation in microglia, decreased the mRNA expression of M1-labeled protein (iNOS), and increased the mRNA expression of M2-labeled protein (Arg1). Flow cytometry revealed a significant change in the ratio of M1/M2 microglia. Additionally, Lac-EVs decreased the secretion of proinflammatory cytokines (IL-1β and IL-6) and increased IL-10 production after LPS stimulation. These findings suggest that Lac-EVs have anti-inflammatory effects and can promote the activation of M2 microglial cells without causing cellular harm, making them a potential therapeutic strategy for alleviating perioperative neurocognitive dysfunction (PND) driven by inflammation.This study investigates the effects of lactobacillus-derived extracellular vesicles (Lac-EVs) on lipopolysaccharide (LPS)-induced microglial cell activation and inflammation in an in vitro neuroinflammation model. The research aims to explore whether Lac-EVs can modulate microglial polarization and reduce neuroinflammation, particularly by promoting the differentiation of M2 microglia and inhibiting proinflammatory cytokine production. The study found that Lac-EVs reduced LPS-induced inflammation in microglia, decreased the mRNA expression of M1-labeled protein (iNOS), and increased the mRNA expression of M2-labeled protein (Arg1). Flow cytometry revealed a significant change in the ratio of M1/M2 microglia. Additionally, Lac-EVs decreased the secretion of proinflammatory cytokines (IL-1β and IL-6) and increased IL-10 production after LPS stimulation. These findings suggest that Lac-EVs have anti-inflammatory effects and can promote the activation of M2 microglial cells without causing cellular harm, making them a potential therapeutic strategy for alleviating perioperative neurocognitive dysfunction (PND) driven by inflammation.