Lung injury induced by acute aortic occlusion with subsequent aortic ischemia-reperfusion is an important factor in the development of postoperative acute lung injury following abdominal aortic surgery (Gelman,1995). Overproduction and/or insufficient removal of reactive oxygen species during ischemia-reperfusion (IR) result in significant damage to cell structure and organ functions. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to exert neuroprotective effect against the oxidative stress in animal models but no studies have yet been conducted to test the protective effects of fluoxetine against the lung injury. The present study aimed to examine whether the fluoxetine would be able to prevent the oxidative damage in lung induced by the occlusion and reperfusion of infrarenal abdominal aorta (IAA). Adult male Wistar rats (300-400g, n=24) anaesthetized with pentobarbital sodium (60 mg kg-1,i.p.) were randomized to 3 groups (n=8). Control (Sham), IR, and Fluoxetine+ IR (F+IR) groups. Control group, underwent laparotomy and dissection of IAA without occlusion. The IR group underwent laparotomy and clamping of the IAA for 60 min followed by 120 min of reperfusion. The rats in the F+IR groups received fluoxetine (20 mg kg-1, i.p. Sigma) once daily for 3 days before ischemic surgery. Thirty minutes after the last injection, the same IR procedure was performed. After withdrawn of blood samples, experiment was terminated by deep anesthesia (Pentobarbital sodium; 150 mg kg-1,i.p.). Bronchoalveolar lavage fluid (BALF) and lung tissue specimens were obtained for biochemical evaluations. Lung tissue oxidative stress was investigated by means of lipid hydroperoxide (LHPO), superoxide dismutase (SOD), pro-oxidant antioxidant balance (PAB), ferric reducing/antioxidant power (FRAP) and malondialdehyde (MDA) levels in lung tissue and BALF. Histological evaluation of the rat lung tissues was also performed. Presented values are means + S.E. compared by ANOVA as post-hoc Tukey. Except SOD and FRAP activities, all markers related to lung oxidative stress (PAB, LHPO and MDA) were significantly increased in the lung tissue (p<0.01, p<0.05, p<0.05 vs control; respectively) and likewise BALF samples of IR group (p<0.05vs control). Pretreatment with fluoxetine prevented the increase in PAB, LHPO activities and MDA levels (p>0.05 vs control). SOD and FRAP activities were significantly reduced in the lung tissue and BALF of IR group (p<0.01, p<0.05 vs control), but fluoxetine pretreatment abolished the effect of IR on SOD and FRAP activities (p>0.05 vs control). Fluoxetine also attenuated IR-induced total histological injury in lung tissue architecture. In conclusion, fluoxetine confers protection against lung IR injury and protective effects seem to be related to the inhibition of oxidative stress and prevention of cellular integrity of lung.