The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has recently been explored in various pathological conditions of the central nervous system (CNS). However, the application of BM-MSCs in acutely induced Alzheimer's disease (AD) has not yet been reported. Herein the feasibility of using the BM-MSCs, as a therapeutic agent for AD has been tested. To assess this possibility, an acutely induced AD model induced by injecting amyloid-β (Aβ) into the dentate gyrus (DG) of hippocampus of C57BL/6 mice was used. Intracerebral transplantation of BM-MSCs into the brain of an induced AD model reduced their Aβ levels when compared to sham-transplanted animals. The diminution of Aβ deposits was accompanied by the activation of microglia. In addition, the activated microglia was located near the Aβ deposits, and their morphology was changed from ramified to ameboid as a sign of microglial phagocytosis. This study provides evidence that BM-MSCs can promote the reduction of Aβ through the microglial activation in this acutely induced AD brain, suggesting a potential therapeutic agent against AD.