Aim: Spinal cord injury (SCI) triggers inflammatory response by activation and accumulation radical oxygen species (ROS). Cell therapy has no effective long term recovery outcomes due to presence of ROS in lesion site increase the death rate of transplanted cells.One efficient approach to address this issue is adding adjuvants like neurotrophic factors and antioxidants, among them melatonin has been reported to play a key role in neuroprotectection. The melatonergic treatment is remarkably associated with scavenger oxidative stress and cell proliferation. The purpose of this study is the impact of preconditioning of human Olfactory ecto-mesenchymal stem cells (hOEMSCs)through melatonin on treatment rat SCI model. Methods: The cells were treated in various concentrations of melatonin (0-100 µM) at different time points (2-48 h). The cell viability was evaluated by MTT. The pretreated cells were injected into the contused rat spinal cord model. Cell integration was estimated by luxal fast blue (LFB) andimmunohistochemistry. Behavioral assessments were conductedon a weekly basis for 7 consecutive weeks. Results: The highest cell viability rate was remarkably seen at 10 μM melatonin at time period 2-12 h. Our LFB and immunohistochemistry results reveals the cavities were partially disappeared in cell-treated groups. The quantity of DiI-labled cells was considerably inclined in group that treated by melatonin. The locomotor and sensory scores were significantly enhanced in MT/hOEMSCs group. Conclusion: These findings may suggest hOEMSCs pretreated by melatonin would have neuroprotective effect which could be applied as a suitable strategy for cell therapy in SCI