Autonomic dysreflexia is an autonomic behavioural condition that manifests after spinal cord injury (SCI) and is characterized by acute, episodic hypertension following afferent stimulation below the level of the injury. Common triggers of autonomic dysreflexia include colorectal distension (CRD), and various somatic stimuli. The development of autonomic dysreflexia is dependent, in part, upon the degree of intraspinal inflammation and the resultant spinal neuroplastic changes that occur following SCI. 17beta-estradiol (E) has neuroprotective, anti-inflammatory and smooth muscle relaxant properties, and is therefore a candidate drug for the treatment and/or prevention of autonomic dysreflexia. Autonomic dysreflexia was assessed in adult male mice treated with E. We investigated whether E could be acting centrally by altering: (1) the size of the small diameter primary afferent arbor, (2) the degree of microglia/macrophage infiltration at the site of the injury, or (3) the amount of fibrous scarring present at the injury site. To determine whether E could be working through uncoupling protein-2 (UCP-2), a protein involved with inflammation and regulated by estrogen in some tissues, autonomic dysreflexia was assessed in E-treated adult male mice lacking UCP-2 (UCP-2 KO). 17beta-estradiol was equipotent at reducing autonomic dysreflexia in both UCP-2 KO and WT mice following CRD but not tail pinch. We have shown that E reduces autonomic dysreflexic responses to visceral but not somatic stimulation in male mice independent of the size of the primary afferent arbour, the degree of chronic inflammation, and the presence of UCP-2.