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Injury to the spinal cord results in immediate physical damage (primary injury) followed by a prolonged posttraumatic inflammatory disorder (secondary injury). The present study aimed to investigate the neuroprotective effects of minocycline and FK506 (Tacrolimus) individually and in combination on recovery from experimental spinal cord injury (SCI). Young adult male rats were subjected to experimental SCI by weight compression method. Minocycline (50 mg/kg) and FK506 (1 mg/kg) were administered orally in combination and individually to the SCI group daily for three weeks. During these three weeks, the recovery was measured using behavioral motor parameters (including BBB, Tarlov and other scorings) every other day for 29 days after SCI. Thereafter, the animals were sacrificed and the segment of the spinal cord centered at the injury site was removed for the histopathological studies as well as for biochemical analysis of monoamines such as 5-hydroxytryptamine (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) and some oxidative stress indices, such as thiobarbituric acid-reactive substances (TBARS), total glutathione (GSH) and myeloperoxidase (MPO). All behavioral results indicated that both drugs induced significant recovery from SCI with respect to time. The biochemical and histopathological results supported the behavioral findings, revealing significant recovery in the regeneration of the injured spinal tissues, the monoamine levels, and the oxidative stress indices. Overall, the effects of the tested drugs for SCI recovery were as follows: FK506 + minocycline > minocycline > FK506 in all studied parameters. Thus, minocycline and FK506 may prove to be a potential therapy cocktail to treat acute SCI. However, further studies are warranted.Minocycline and FK506 in combination as well as individually were tested in SCI rats.All behavioral motor functions improved in SCI animals due to drugs treatment.Histopathological recovery was observed due to drugs treatment in the SCI animals.Neurotransmitters and oxidative stress were also improved in the SCI tissues.Recovery was in the order of FK506 + minocycline > minocycline > FK506 throughout.