Acute spinal cord injury (SCI) results in long-lasting functional impairments through both mechanical damage as well as secondary mechanisms, with limited available therapeutic options. β-Carotene has been demonstrated to exert biological and pharmacological activities. We aimed to examine the protective effects of β-carotene in a SCI rat model. We tested the hind-limb locomotor function, neuro-inflammation, oxidative stress, astrocyte activation and nuclear factor–κB (NF-κB) pathway activation of SCI rats, with or without β-carotene treatment. β-Carotene substantially improved locomotion that was reduced by SCI. β-Carotene also relieved SCI-induced oxidative stress via regulation of reactive oxygen species, malondialdehyde, nitric oxide, and superoxide dismutase, as well as restored SCI-suppressed protein expressions of Nrf2 and HO-1. Additionally, β-carotene decreased the generation of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-18 and cyclooxygenase-2, and inhibited the activation of astrocyte in the spinal cord. Furthermore, β-carotene treatment markedly inhibited the NF-κB pathway activation. Our findings demonstrated that β-carotene effectively reduced the progression of secondary injury events following SCI through preventing NF-κB pathway activation. Therefore, β-carotene may be an effective candidate for treating SCI.