Potassium channels have re-emerged as targets for overactive bladder and other urological diseases in recent years (Gopalakrishnan & Shieh, 2004). Large conductance Ca⁺² activated potassium (BK) channels are thought to have a prominent role in urinary bladder smooth muscle function and have become a potential treatment target of overactive bladder (Meredith et al, 2004).The aim of this study was to investigate the role of BK channels in inhibiting the muscarinic stimulated contractions of bladder smooth muscle in the streptozotocin-induced diabetic rat. Male Wistar rats (200-250g) were administered streptozotocin (STZ, 65mgkg-1, i.p.). Strips of detrusor smooth muscle were isolated from bladder of rats 1, 4, and 12 weeks after STZ or from weight matched controls. Tissues were mounted in tissue baths containing Krebs-bicarbonate solution (in mM, 118.3 NaCl, 11.7 D-Glucose, 24.9 NaHCO₃, 4.7 KCl, 1.15 MgSO₄, 1.15 KH2PO₄, 1.9 CaCl₂) with 5µM indomethacin at 37°C and gassed with 95% O₂/5% CO₂. Isometric tension was measured via UF1 force transducers connected to a Powerlab using Chart software. After equilibration, (2g of tension for 60 minutes), tissues were stimulated with 1μM carbachol (CCH) twice with a fifteen minutes wash in between. The tissues were then stimulated with CCH in the presence of increasing concentrations of the BK channel opener, NS1619 (1-30μM) or the vehicle (DMSO) to measure the inhibitory effect. Differences between control and diabetic tissues were assessed using Students t-test. NS1619 significantly (p<0.01 and p<0.05) inhibited the CCH induced contractions only at 30μM in control (19.62.80±3.2%) (n=18), 1 (22.25±6.0%) (n=7), 4 (15.82±3.6%) (n=12), and 12-week (27.79±4.7%) (n=12) diabetic tissues, producing a similar level of inhibition in all groups. However, in 12-week diabetic tissue, NS1619 also significantly inhibited the contractions at 10μM (14.37.37±3.1%) (p<0.05) showing higher sensitivity. In conclusion, NS1619 did have a minor inhibitory effect on agonist induced contractions only at its highest concentration (30μM) in control and diabetic groups. But it seems that 12-week diabetic tissues are more sensitive to this inhibition which requires further investigation. These results suggest that BK channel modulation can affect detrusor contractions in this rat model. But the mechanisms underlying this modulation need further investigation.