In this study, neuroprotective effect of tamoxifen has been explored in spinal cord injury (SCI) in rats by examining factors influencing IKK/NF-kB pathway in SCI in rats. It has been shown in several studies that IKK/NF-kB signaling pathway plays a key role in pathophysiology of SCI. In this study, three groups of rats (n = 17 each) were selected that included, tamoxifen group (here tamoxifen was injected after SCI in rats), SCI group (here only dimethylsulfoxide was administered after inducing SCI in rats) and sham group (here only laminectomy was performed). The effect of tamoxifen (5 mg/kg) on various factors responsible for activation of IKK/NF-kB signaling pathway including NF-kB p65, phosphorylated I-kB alpha was studied through Western blotting as well as densitometry. The examination of expression of active caspase-3 and myeloperoxidase activity was also carried out through Western blot analysis and densitometry. A comparison of three groups of rats showed that administration of tamoxifen significantly reduced the expression of NF-kB p65 and phosphorylated I-kB alpha (P < 0.05) compared to control. It also attenuated the expression of active caspase-3 resulting in the reduction of apoptosis, and infiltration of leukocytes to the injury site was also greatly reduced in the group where tamoxifen was administered. Statistical analysis through SPSS 13.0 software showed a significant decrease in the expression of inflammatory factors in groups where tamoxifen was administered. We conclude that tamoxifen possesses the potential neuroprotective effects that can be explored further for future therapeutic techniques in treating spinal cord injuries.