Aescin has many physiological functions that are highly relevant to spinal cord injury (SCI), including anti-inflammation, anti-oxidation, anti-oedema, and enhancing vascular tone. The present study investigated the putative therapeutic value of aescin in SCI, with a focus on its neuroprotective, anti-inflammatory, and anti-oxidative properties. Sodium aescinate (1.0 mg/kg body weight) or equivalent volume of saline was administered 30 min after injury by intravenous injection, with an additional dose daily for seven consecutive days after moderate SCI in rats. After contusion injury of the 8th thoracic (T8) spinal cord, aescin-treated rats developed less severe hind limb weakness than saline controls, as assayed by the Basso-Beattie-Bresnahan scale, the beam walking test, and a footprint analysis. The improved locomotor outcomes in aescin-treated rats corresponded to markedly decreased immune response, oxidative stress, neuronal loss, axon demyelination, spinal cord swelling, and cell apoptosis, measured around T8 after impact. Our data suggest aescin treatment as a novel, early, neuroprotective approach in SCI. Given the known safety of aescin in clinical applications, the results of this study suggest that it is a good candidate for SCI treatment in humans.