【】Objective To investigate the effect of rat mesenchymal stem cell (MSC) on D-galactose-induced brain tissue aging and its potential mechanism of action. Methods The rat? brain aging model was established by injecting D-galactose, and the experimental group received MSC injections via the tail vein. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in rat brain tissue at the end of the experiment, and changes in pathological sections of brain tissue were observed by HE staining. Finally, the expression of inflammatory factors Interleukin-1(IL-1) and Interleukin-6 (IL-6), pathway proteins brain-derived neuotrophyic factor (BDNF)-TrkB (Tropomyosin receptor kinase B), negative growth regulators p53 and p16, as well as vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF) were uniformly observed by PCR with Western blot. Results Compared with the model group, SOD activity in the brain tissue of rats in the experimental group was significantly increased, while MDA level was significantly decreased (P < 0.05). HE staining pathological images showed that the experimental group was able to improve the pathological state of the cerebral cortex and hippocampus, and increase the number of neurons and nucleus pulposus ratio in the brain. Meanwhile, PCR and Western blot results showed that the expression of IL-1 and IL-6, p53 and p16 was significantly decreased, while the expression of BDNF and TrkB, VEGF and bFGF was significantly increased in the experimental group compared with the model group (P < 0.05). Conclusion Taken together, our data suggest that MSCs potentially mitigate D-galactose-induced cerebral senescence by concurrently modulating the BDNF-TrkB axis to attenuate oxidative/inflammatory damage while enhancing secretion of vasculotrophic (VEGF) and neurotrophic (bFGF) factors for neuronal maintenance.