Bladder dysfunction is among the most drastic and quality-of-life-reducing conditions after spinal cord injury (SCI). Neuroinflammation in the lower urinary tract (LUT) after SCI could be a key driver of neurogenic bladder dysfunction and tissue fibrosis. Leukotrienes, a group of highly active lipid mediators, are potent inflammatory mediators. Here, we explored the potential of early montelukast (MLK) therapy, a cysteinyl leukotriene receptor 1 antagonist, on LUT function and structure four weeks after severe SCI in rats. Rats (strain Lewis, female, n = 50) received a permanent bladder catheter, followed by a complete T9 spinal cord transection. MLK was given daily, starting on day one post-injury. Bladder and locomotor function were regularly assessed. Bladder tissue was histologically and immunhistochemically analyzed. Post-SCI, MLK concentrations in plasma and cerebrospinal fluid were clinically relevant. MLK improved bladder functionality. MLK had no impact on smooth muscle alignment and uroepithelial integrity at this early SCI time point. This pilot study gave first insights into early, continuous oral MLK treatment with the first promising results of preserved LUT function and possible subsequent improved tissue integrity.