Background Ischemic stroke has been regarded as a major cause of disability and death around the world due to limited effective therapies. Accumulating evidence have shown that although microglia are polarized to an anti-inflammatory M2 phenotype in the early stage of ischemia, they transform progressively into a proinflammatory M1 phenotype. Bone marrow-derived mesenchymal stem cells (BMSCs) may be used to treat ischemic injury through regulating the poststroke inflammatory response. However, the mechanism by which BMSCs can treat ischemic stroke remains unclarified. Objective This study aimed to investigate whether BMSCs shift M1-to-M2 phenotype transformation of microglia/macrophages and enhance neurogenesis in a rat transient middle cerebral artery occlusion (tMCAO) model. Methods Ninety-minute tMCAO was applied to the rats, followed by reperfusion. BMSCs were transplanted into the rats via intravenous injection at 24 h after tMCAO. After being randomly divided into the sham group, the MCAO group, and the BMSCs group, the rats’ behavior was assessed at 1, 3, 7, and 14 days following tMCAO. qRT-PCR, double-immunofluorescence staining, and Western blot were performed at 3 and 14 days after tMCAO to determine M1/M2 polarization of microglia/macrophages. Neurogenesis was examined by double-immunofluorescence staining at 14 days after tMCAO. Expression of brain-derived neurotrophic factor (BDNF) was measured on the protein level by immunofluorescence staining at 3 and 14 days after tMCAO. Results We found that BMSCs treatment promoted the recovery of neurological function after tMCAO, inhibited the expression of TNFα, iNOS and CD16/32, which are markers of M1 microglia/macrophage, and enhanced the expression of IL10, TGFβ and CD206 that are markers of M2 microglia/macrophage. Moreover, BMSCs treatment promoted neurogenesis and M2-derived BDNF expression after tMCAO. Conclusion It is indicated by the results that BMSCs modulate neuroinflammation and enhance neurogenesis, which could be due to transforming microglia/macrophages from the M1 polarization state towards M2 in a rat tMCAO model.