Abstract: Endoluminal devices and methods that facilitate treatment of a desired treatment region of the gastrointestinal tract, in particular the duodenum, are provided herein. Such devices include a catheter having a treatment delivery portion disposed between proximal and distal balloons. The treatment can include thermal ablation of the treatment region by delivering a treatment fluid to the treatment region between the inflated balloons. In one aspect, the treatment fluid is delivered so as to fill the entire treatment region between the balloons without regard to the inflated balloon pressure. To ensure filling, the treatment fluid can be delivered into the treatment region until a pressure increase is observed or until a pre-determined volume is delivered. Other treatment devices and methods include means of uniformly distributing a treatment gas for plasma ablation, electrical ablation energy or a chemical or drug eluting stent.