AIMS: Diabetic bladder dysfunction (DBD) is a prevalent diabetic complication thought to progress from overactive (OAB) to underactive (UAB) bladder. Previously we found OAB at 15 weeks in the Akita mouse, a genetic model of Type 1 diabetes. The first aim of this study assesses bladder function at 30 weeks to assess progression. In addition, inflammation triggered by the NLRP3 inflammasome is implicated in DBD. In a second aim we assessed a role for NLRP3 by crossing Akita mice with NLRP3-/- mice. MAIN METHODS: Akita mice were bred with NLRP3-/- mice. The effect of diabetes was assessed by comparing nondiabetic to diabetic mice (all NLRP3+/+). The effect of diabetes in the absence of the NLRP3 inflammasome was assessed by comparing nondiabetic/NLRP3-/- to diabetic/NLRP3-/- mice. Mice were assessed at 30 weeks for blood glucose (glucometer), inflammation (Evans blue), bladder morphology (histology) and bladder function (urodynamics). KEY FINDINGS: At 30 weeks blood glucose of nondiabetics and diabetics was not affected by the presence of absence of NLRP3. Diabetic/NLRP3+/+ mice showed bladder inflammation and detrusor hypertrophy which was blocked in the diabetic/NLRP3-/- mice, clearly showing a role for NLRP3. When bladder function was examined, diabetic/NLRP3+/+ showed an increase in voiding volume and a decrease in frequency, two signs of underactive bladder. However, in the NLRP3-/- mice, diabetes was unable to effectuate these changes, demonstrating that NLRP3-induced inflammation is responsible for UAB symptoms in these mice. SIGNIFICANCE: Akita diabetic mice progress from OAB to UAB. NLRP3 is a possible target to treat DBD.