en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <strong>Introduction:</strong> Spinal Cord Injury (SCI) is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss, and severe functional deficits. Neurotrophic factors are a potential treatment for reducing secondary damage, promoting axon growth; they are responsible for inducing myelination after injury. Olfactory Ensheathing Cells (OECs) and minocycline have promoted locomotor function after SCI. The present study investigated the neuroprotective effects of combined treatment with minocycline and OECs on spinal cord injury related to Brain-Derived Neurotrophic Factor (BDNF) and Glial Derived Neurotrophic Factor (GDNF) expressions after SCI.<br> <strong>Methods:</strong> Adult female rats were used to experimental SCI by weight compression method. Rats received an intraperitoneal minocycline injection (90 mg/kg) immediately after SCI and 24 h after injury. OECs were transplanted one week after the injury. The hindlimb function was assessed using Basso Beattie Bresnahan (BBB) locomotor rating scale and Electromyography (EMG). After 5 weeks, the spinal cord segment centered at the injury site was removed for histopathological analysis. Immunohistological and western blot assays were performed to observe the expression of NeuN, BDNF, GDNF, and Myelin Basic Protein (MBP).<br> <strong>Results:</strong> SCI induced the loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline+OECs increased the score of the BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results suggested that NeuN expression significantly increased in the minocycline+OECs group than other groups. Moreover, electromyography amplitude in treated rats was increased compared to the control group. BDNF, GDNF, and MBP expressions and the number of ventral motor neurons increased further by minocycline+OECs in SCI rats.&nbsp;<br> <strong>Conclusion:</strong> The present study provides evidence that minocycline may facilitate recovery of locomotor function by OECs by increasing BDNF and GDNF expressions following SCI. Olfactory ensheathing cells, Minocycline, Spinal cord injury, Myelin basic protein, Brain-derived neurotrophic factor, Glial derived neurotrophic factor, Electromyography 777 788 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1727-1&slc_lang=en&sid=1 Soheila Pourkhodadad s.porkhodadad@yahoo.com 13700319475328460039305 13700319475328460039305 Yes Department of Animal Physiology, Faculty of Biology, Kharazmi University, Tehran, Iran. Shahrbanoo Oryan shahrbanoo_o@yahoo.com 13700319475328460039306 13700319475328460039306 No Department of Animal Physiology, Faculty of Biology, Kharazmi University, Tehran, Iran. Mohammad Mehdi Hadipour mm_ hadipour_yahoo.com 13700319475328460039307 13700319475328460039307 No Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Gholamreza Kaka gh_kaka@yahoo.com 13700319475328460039308 13700319475328460039308 No Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Seyed Homayoon Sadraie sh_ sadraei@yahoo.com 13700319475328460039309 13700319475328460039309 No Department of Anatomy, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.