Purpose: The pathophysiology of detrusor underactivity remains unclear and impaired bladder afferent function is considered one of the important etiologies. We investigated urothelial barrier deficits, suburothelial inflammation and sensory proteins expressed in the bladder mucosa of patients with detrusor underactivity. Materials and Methods: Bladder mucosa biopsies were performed in 34 patients with videourodynamic proven detrusor underactivity as the study group and in 10 women with stress urinary incontinence as controls. The expression of zona occuldens-1, E-cadherin in the urothelium, tryptase and apoptosis levels in the suburothelium, b3-adrenoceptor, M2 and M3 muscarinic receptors, P2X3 receptor, and inducible and endothelial nitric oxide synthase were compared between study patients and controls. Results: Study patients included 22 women and 12 men with a mean +/- SD age of 56.3 +/- 19.7 years, of whom 15 had a history of diabetes. Study patients had significantly lower E-cadherin expression, and a higher number of mast cells and apoptotic cells than controls. Additionally, lower expression of M2 and M3 muscarinic receptors, P2X3 receptors and endothelial nitric oxide synthase was detected in study patients but higher expression of b3-adrenoceptor. In study patients a positive correlation was noted between tryptase and apoptosis levels (r = 0.527) and between the expression of M2 muscarinic receptor and P2X3 receptor (r = 0.403). However, b3-adrenoceptor expression negatively correlated with E-cadherin expression (r = -0.490, each p < 0.05). Conclusions: Urothelial dysfunction, increased suburothelial inflammation and altered sensory protein expressions in bladder mucosa were prominent in patients with detrusor underactivity. Impaired urothelial signaling and sensory transduction pathways appear to reflect the pathophysiology of detrusor underactivity.