Bradykinin (BK) is an endogenous peptide with diverse biological actions and is considered an important mediator of the inflammatory response in both the peripheral and the central nervous systems. BK has attracted recent interest as a potential mediator of K⁺ conductance, Cl^- channels and Ca²⁺-activated K⁺ channels, however, a few reports have associated BK with the voltage-gated K⁺ current. In this study, we demonstrated that BK suppressed the transient outward potassium current (I_A) in mouse Schwann cells using whole-cell recording techniques. At a concentration of 0.1 nM to 5 µM, BK reversibly inhibited I_A in a dose-dependent manner with the modulation of steady-state activation and inactivation properties. The effect of BK on I_A current was abolished after pre-incubation with a B2 receptor antagonist, but could not be eliminated by B1 receptor antagonists. Intracellular application of GTP-S induced an irreversible decrease in I_A, and the inhibition of Gs using NF449 provoked a gradual augmentation in I_A and eliminated the BK-induced effect on I_A, while the Gi/o antagonist NF023 did not. The application of forskolin or 8-Br-cAMP mimicked the inhibitory effect of BK on I_A, and abolished the BK-induced effect on I_A. H-89, an inhibitor of PKA, augmented I_A amplitude and completely eliminated the BK-induced inhibitory effect on I_A. In contrast, activation of PKC by PMA augmented I_A amplitude. A cAMP assay revealed that BK significantly increased intracellular cAMP level. It is therefore concluded that BK inhibits the I_A current in SCs by cAMP/PKA-dependent pathways via activation of the B2 receptor.