Thiswork aimed to study protective effects of oral administration of wheat germ oil (WGO 500 mg/kg B.wt) on hyperlipidemia and brain oxidative stress in hypercholesterolemic (HC) and streptozotocin (STZ) -diabetic rats. Five groups of male Sprague Dawely rats were used; group 1: control negative, group 2: HC rats, group 3: STZ- diabetic rats, group 4: HC rats treated with 500mg/kg B.wt WGO and group 5: STZ-diabetic rats treated with 500mg/kg B.wt WGO. After 6 weeks (the end of the experimental period), serum of all rat groups were used for lipid profile analysis to determine the levels of total cholesterol (TC), triacylglycerol (TAG), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), TGs/HDL-C ratio and TC /HDL-C ratio. Brain tissue homogenates from all rat groups, were used for evaluation of malondialdehyde (MDA) level, antioxidant enzymes activities like superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). Specimens from cerebrum were microscopically examined. HC rats (G2) and STZdiabetic rats (G3) showed a significant elevation of serum lipid profile, atherogenic index (AI) and brain MDA level, while there was a significant decrease in serum HDL-C and antioxidant enzymes activities in brain tissue homogenate when compared with control negative group (G1). Oral administration of 500mg/kg B.wt WGO to HC and STZ-diabetic rats, significantly (p ˂ 0.05) reduced serum lipid profile, AI and brain MDA, however significantly (p ˂ 0.05) increased serum HDL-C levels and antioxidant enzymes activities in brain tissue homogenate when compared with untreated HC and STZ- diabetic rats. Histopathological examination of cerebral tissue revealed that WGO treatment of HC and STZ-diabetic rats showed normal histology. Abbreviations: WGO, wheat germ oil; B.wt, body weight; TC, Total cholesterol; STZ, streptozotocin. TGs, Triglycerides; LDL-C, Low density lipoprotein- cholesterol; VLDL-C, Very low density lipoprotein- cholesterol; HDL-C, High density lipoprotein-cholesterol; AI, Atherogenic Index ; MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GSH, reduced glutathione; PBS, phosphate buffer saline; H&E, hematoxylin and eosin