Purpose. This study was intended to investigate the effect of dexmedetomidine on oxidative stress response in pneumoperitoneum established in rats. Methods. Animals were randomized into three groups, group S: with no pneumoperitoneum, group P: with pneumoperitoneum established, and group D: given 100 mcg intraperitoneal dexmedetomidine 30 min before establishment of pneumoperitoneum. Plasma total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) activity were measured 30 min after conclusion of pneumoperitoneum. Results. The mean TOS level was significantly higher in group P than in the other two groups, and the TOS level was significantly higher in group D than in group S (P < 0.05). Plasma TAS level was found to be lower in group P than in the other two groups, and the TAS level was lower in group D than in group S (P < 0.05). Consequently, the OSI was significantly higher in group P than in groups D and S (P < 0.05). Conclusions. Ischemia-reperfusion phenomenon that occurs during pneumoperitoneum causes oxidative stress and consumption of plasma antioxidants. Dexmedetomidine decreases oxidative stress caused by pneumoperitoneum and strengthens the antioxidant defense system.