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Aim: To investigate the effects of peripheral orexins on myoelectric activity of the sphincter of Oddi (SO) in fasted rabbits, and carry out a preliminary investigation into the mechanisms underlying these effects, Methods: Myoelectric activity of SO in fasted rabbits was recorded before and after intravenous or local application of orexins. The effects of intravenous atropine on orexin-increased myoelectric activity of SO were tested. Results: Myoelectric activity of SO was activated by both intravenous and local injection of orexin-A or orexin-B. Intravenous application of atropine completely inhibited the excitatory effect of orexins on SO.Conclusion: Peripheral application of orexins can increase myoelectric activity of SO in fasted rabbits, which is partially associated with the activation of the cholinergic pathway.