Background: Diaphragm fatigue (DF) has been implicated in respiratory failure in diseases that increase inspiratory resistance loading (IRL) and may complicate weaning of patients from mechanical ventilation. Objective: The purpose of this study was to examine the effects of dobutamine administration (10 μg/kg/min) on DF and to identify the mechanisms by which dobutamine augments diaphragm shortening and diaphragm blood flow (DBF) during fatigue with a rat model. Methods: The study had an experimental design with 3 groups of Sprague-Dawley rats (n = 38) with 4 experimental periods: period 1, control; period 2, application of IRL; period 3, treatment; and period 4, recovery.