<p>Mesenchymal stem cells (MSCs) have emerged as a promising alternative for treating neurological disorders due to their neuroprotective, neuroregenerative, immunomodulatory, anti-inflammatory, and anti-apoptotic properties. The use of allogeneic MSCs offers advantages such as the selection of specific cells and their immediate availability. This study aimed to evaluate the safety and feasibility of intrathecal transplantation of allogeneic equine bone marrow-derived MSCs (EqBM-MSCs) in healthy horses. Ten healthy horses (five–12 years old) were randomly divided into two groups. In the control group (<i>n</i> = 5), phosphate-buffered saline was administered intrathecally, while the MSCs group (<i>n</i> = 5) received 3 × 10⁶ allogeneic EqBM-MSCs. Safety and feasibility were assessed through physical examinations monthly for one year, cerebrospinal fluid (CSF) analysis before and six days after transplantation, and magnetic resonance imaging (MRI) one-year post-transplantation. No significant differences were found between the groups in physical examinations or CSF analysis before and six days after transplantation. Furthermore, MRI showed no changes after one year. Matrix Metalloproteinase-2 (MMP-2) expression was detected in the CSF before and after transplantation but showed no significant differences. These findings suggest that intrathecal transplantation of allogeneic EqBM-MSCs is safe and viable, offering a potential therapeutic approach for neurological disorders in horses.</p>