Objective To investigate the therapeutic effect of tacrolimus on spinal cord injury rats and its regulation of the NF-κB/ JNK pathway. Methods Rats were randomly divided into three groups ( n = 15): sham group, model group and tacrolimus administration group. The animal model of spinal cord injury was established by Allen’ s method. The rats were given tacrolimus (0. 3 mg / kg) once a day for 21 days. Basso, Beattie and Bresnahan (BBB) scores were tested on days 0, 1, 7, 14 and 21. Hematoxylin and eosin staining was used to observe the state of spinal cord injury in rats; SOD, CAT, and GPX activity and MDA content in spinal cord tissue were measured by a kit; IL-4 and TGF-beta expression in spinal cord tissue was measured by RT-PCR; NF-κB p-p65, NF-κB p-p65, JNK and p-JNK protein expression was measured in spinal cord tissue by western blots. Results Tacrolimus could significantly improve the BBB score of spinal cord injury rats (P < 0. 05), increase SOD, CAT, GPX activity, decrease MDA content, reduce abnormal apoptosis of spinal cord neurons, and decrease the expression of IL-4 and TGF-beta and the NF-κB, p-p65 and p-JNK/ JNK protein ratios. Conclusions Tacrolimus can significantly improve spinal cord injury, and the mechanism may be related to its anti-oxidative, anti-inflammatory response, and anti-apoptosis activities in spinal cord neurons and inhibition of NF-κB/ JNK signaling pathway activation.