Female Sprague-Dawley rats (11-12 weeks) were used, and DM was induced using a single intraperitoneal injection of STZ (65 mg/kg). We divided rats into four groups: (1) non-DM (N) group, (2) DM with low-dose insulin (DI) group, (3) non-insulin DM with vehicle (D) group, and (4) non-insulin DM with sGC (GC) group. In insulin-treated DM rats (Group DI), slow-releasing insulin pellets (2 units/24 hours) were implanted 3 days after inducing DM. In Group GC, a sGC activator (BAY 60-2770,1 mg/kg/day) was orally administered from 6 to 8 weeks after inducing DM. First, in Groups DI and D, we performed 24-h voiding assay at 2, 4, and 8 weeks, cystometry and urethral perfusion pressure (UPP) recordings at 8 weeks with or without low-dose insulin treatment, and compared the data with those in Group N. In cystometry, we measured opening pressure (OP, pressure at which the urethra opens and urine flow starts), intercontraction intervals (ICI), the number of non-voiding contractions (NVCs) per minute, postvoid residual (PVR), bladder capacity, bladder compliance, and voiding efficiency . NVC was defined as an increase in intravesical pressure of more than 8 cmH2O above the baseline. In UPP recordings, we measured urethral pressures (UP) at which urethra started to relax (UPUR), UP nadir which is the lowest pressure during urethral relaxation, UP reduction which is difference between UPUR and UP nadir, and high-frequency oscillation (HFO) amplitude of UP during voiding . Secondly, we evaluated the effects of sGC treatment on the cystometric and UPP parameters at 8 weeks of DM in Groups D and GC. Thirdly, in a separate group of animals, the urethra and the bladder were harvested at 8 weeks of DM to evaluate the mRNA levels various markers using real-time PCR, which included NO-related markers such as phosphodiesterase type 5 (PDE5), multidrug resistance protein 5 (MRP5) and Ca2+ channels, ischemia markers such as hypoxia-inducible factor 1 alpha (HIF-1α), and inflammatory markers such as transforming growth factor beta 1 (TGF-β1) and tumor necrosis factor alpha (TNFα). All values are expressed as means ± standard deviations. We used the Kruskal-Wallis one-way analysis of variance to analyze statistical differences and Dunn’s post hoc test between in Groups N, DI, and D, and the Mann Whitney U test to evaluate statistical differences between in Groups D and GC. A P-value < 0.05 was considered statistically significant.