Oxidative stress and reperfusion injury may develop in different ischemia-reperfusion (IR) models. Growing evidence links altered lipid protein redox-homeostasis with IR. The effect of fluoxetine (FLX; N-methyl-3-[4-(trinuoromethyl) phenoxyl benzenepropanamine), on the lipid protein redox-homeostasis mechanisms in the rats exposed to aortic IR is unclear. We aimed to investigate the effects of FLX on circulating protein oxidation and lipid peroxidation parameters, such as ischemia modified albumin (IMA), lipid hydroperoxide (LOOH), prooxidant antioxidant balance (PAB), erythrocyte glutathione (GSH). CuZnsuperoxide dismutase (CuZn-SOD), ferric reducing antioxidant power (MAP), as potential IR biomarkers. Wistar rats were randomized into three groups ([7= 7/group): 1) Control (sham laparotomy); 2) IR without FLX, (60 min ischemia and 120 min reperfusion); 3) IR with FLX ([FLX I IR) (FLX 20 mg/kg/day, i.p, for three days before surgery). All of the aforementioned parameters (IMA, LOOH, PAD, GSH, CuZn-SOD, and [RAP) were measured spectrophotometrically. IMA, LOOH, and PAD levels in IR group were significantly higher than the control (P < 0.01 respectively) and fluoxetine groups (P < 0.01, P < 0.01, and P < 0.05 respectively), whereas CuZn-SOD activities, GSH and FRAP were significantly lower in IR groups. Fluoxetine group significantly reduced IMA when compared to IR group (P < 0.001) and control group (P < 0.01). With respect to IMA, LOOH and PAB, impaired redox homeostasis is substantially more prominent in aortic IR. The antidepressant FD( has profitable effects on circulating redox status in rats exposed to aortic IR. FLX administration before IR might decrease the surgery-enhanced free radical production; taken together, the antioxidant effects of FLX supplementation should be considered in future studies. (C) 2015 Elsevier By. All rights reserved.