Background: Intracerebral hemorrhage (ICH) stands as a crucial cerebrovascular pathology, wherein subsequent neuroinflammatory reactions augment neuronal detriment. Microglia, the principal immune effectors within the central nervous system, significantly influence the inflammatory cascade following ICH. Interleukin (IL)-10 is an anti-inflammatory cytokine that functions via the IL-10 receptor (IL-10R). It has been demonstrated to facilitate M2 polarization of microglial cells, thereby aiding in the resolution of inflammation and the repair of neural tissue. However, the specific mechanism of IL-10R in regulating microglial polarization remains unclear. Therefore, this study aimed to elucidate the role of IL-10R in facilitating microglia differentiation into the M2 phenotype, specifically focusing on its modulation of the toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) signaling pathway. Methods: We established a mouse model of intracerebral hemorrhage (ICH) to investigate the impact of neural stem cell (NSC) transplantation. IL-10R knockdown was achieved through cell transfection. The expression levels of inducible nitric oxide synthase (iNOS) and the mannose receptor (CD206) were evaluated using Western blot analysis to assess microglial polarization. Furthermore, we quantified inflammation levels by assessing the expressions of IL-10R, IL-1β, and tumor necrosis factor-alpha (TNF-α) using enzyme-linked immunosorbent assay (ELISA). Assessment of motor function was conducted using the modified neurological severity score (mNSS) and the rotarod performance test. Neuronal injury and mortality were determined by measuring brain water content, conducting Nissl staining, and performing the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Additionally, Western blot analysis was employed to evaluate the activity of the toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway, with its activation being suppressed by the specific inhibitor Resatorvid (TAK-242). Results: We found that NSC transplantation significantly decreased microglial M1 polarization, inflammatory response, brain water content, neuronal cell damage, and apoptosis while increasing microglial M2 polarization and mice motor function following ICH. Inhibition of IL-10R reversed the effect of NSC transplantation, indicating its crucial role in NSCs-mediated neuroprotection. Furthermore, the activity of the TLR4/NF-κB inflammatory pathway was enhanced after ICH, which was suppressed by NSCs. Following NSC treatment, the IL-10R inhibition activated the TLR4/NF-κB pathway, which was reversed by TLR4/NF-κB pathway inhibitor TAK-242. Additionally, IL-10R inhibition counteracted the effect of NSC transplantation, which was disrupted when the TLR4/NF-κB pathway was inhibited. Conclusion: This study suggests that IL-10R plays a crucial role in NSC transplantation for treating ICH. Inhibiting the TLR4/NF-κB pathway facilitates M2 polarization of microglial cells, leading to a decrease in neuroinflammatory response. This finding provides a new molecular target for treating ICH and other neuroinflammatory diseases. It emphasizes the potential therapeutic value of NSC transplantation in conjunction with the modulation of IL-10R signaling.