Background. Movement disorders and atrophy occur in the diaphragm, the most important muscle of respiration, because of mechanical ventilation (MV). Objectives. In this animal model, we aimed to evaluate the effect of intravenous theophylline administration on the prevention of mechanical ventilation-induced diaphragmatic atrophy. Material and Methods. In our study, 30 healthy male Sprague-dawley rats were used. They were divided into 3 equal groups. Group 1: the control group (no MV); group 2: the placebo group that received MV; Group 3: the theophylline group composed of rats that received both MV and theophylline therapy. In all 3 groups, the diaphragmatic atrophy was evaluated histopathologically. Results. In the histopathological examination, no macroscopic thickening and microscopic atrophy were observed in the diaphragm in the control group. In the placebo group (group 2), macroscopically definite thickening was observed in all rats, and microscopically, heavy (+++) atrophy was observed. In the theophylline group (group 3), there was no atrophy in one rat. In 8 rats, light (+), and in 1 rat medium (++) atrophy was observed. Conclusions. In our study, it was shown that atrophy occurred in the diaphragms of rats after MV, and the atrophy was decreased after theophylline administration (Adv Clin Exp Med 2014, 23, 1, 33-38).