OBJECTIVE To determine the effects of sudden intra-abdominal pressure (IAP) changes on the terminal ileum in a pneumoperitoneum model. DESIGN An experimental controlled study. SETTING University hospital in Turkey. ANIMAL(S) Thirty-two adult female Sprague-Dawley rats. INTERVENTION(S) The rats were divided into four groups. Group 1 was not subjected to IAP. In group 2, IAP insufflation was performed continuously to keep the IAP at 10 mmHg. Groups 3 and 4 underwent an insufflation-desufflation procedure: group 3 was fluctuated 5 times, and group 4 was fluctuated 10 times within the pneumoperitoneum period of 60 minutes. Thirty minutes after the desufflation, the terminal ileum was removed for the measurement of tissue malondialdehyde (MDA) values and histopathological examination. MAIN OUTCOME MEASURE(S) The tissue MDA values and histopathological damage scores. RESULT(S) The tissue MDA values in the IAP groups (groups 2, 3, and 4) were significantly increased when compared with those of the control group. The mean MDA value in group 4 was higher than that in groups 2 and 3. Histopathologic oxidative damage scores in the mucosa and submucosal layers were significantly higher in groups 2 and 3, compared with those of the control group. However, the highest histopathologic damage scores were observed in group 4. CONCLUSION(S) Unexpected desufflation-insufflation even at normal IAP levels during laparoscopy leads to significant oxidative stress-induced damage in the terminal ileum.