We studied the effects of clonidine (0.5 mg/kg) on hormonal stress response and antioxidant enzymes cold restraint-induced gastric lesions in rats. Rats in the study group were given 0.5 mg/kg intraperitoneal clonidine (n = 12), whereas the control group received 0.5 mL/kg intraperitoneal isotonic sodium chloride solution (n = 9). Animals were then subjected to immobilization at 4 degrees C in restraining devices for 4 h after a starvation period of 24 h. Gastric lesion index, gastric tissue malondialdehyde activity, and plasma cortisol concentrations were assayed. Histopathologic examination demonstrated a stress ulcer index of 3.17 +/- 0.92 mm in the clonidine group and 14.0 +/- 3.22 mm in the control group (P < 0.05). The tissue malondialdehyde concentrations were slightly higher in the control group than in the clonidine group, but the differences were not statistically significant (P > 0.05). Plasma cortisol levels were lower in the clonidine group (P < 0.05). We concluded that clonidine attenuated the tissue damage and stress response in stress-induced gastric ulceration. Implications: Stressful circumstances can cause stomach ulcers, which can bleed, exposing patients to potentially life-threatening complications. In the present animal study we showed that clonidine, a routinely available medication, may be useful in preventing stress-induced stomach ulcers.