Objective: Metabolic syndrome is a disease characterized by hypertension, dyslipidemia and insulin resistance, and constitutes an important risk factor for cardiovascular disorders. The effect of evening primrose oil (EPO) on insulin, adiponectin and resistin levels in brain tissue was investigated in a fructose- related metabolic syndrome model. Materials and Methods: The rats were divided into 4 groups as control, evening primrose oil (orally at a dose of 0.1 mLrat/day), fructose (20% fructose added), fructose+evening primrose oil for 57 days. At the end of the experiment, brain samples were taken and homogenized. Then, insulin, adiponectin and resistin in brain tissue levels were determined by ELISA. Results: Plasma insulin and resistin levels of the fructose group increased (p≤0.05) compared to the controls, on the contrary, adiponectin levels were significantly decreased (p≤0.05) in the fructose group. When EPO was given to rats given fructose, increased insulin and resistin levels decreased (2.54± 0.28a, 2.12±0.68a), (2.21±0.26b, 2.04±0.21a) while decreased adiponectin levels were increased (0.64±0.42c, 1.02±0.35b). Conclusion: It was observed that the impaired metabolic changes caused by fructose in the brain tissue were partially improved in the EPO-treated group as a result of the decrease in insulin, resistin and increase in adiponectin. Accordingly, since metabolic changes in the brains of rats fed with high fructose content may also occur in humans with fructose intake from various foods, the use of EPO in the medical setting may be recommended by clinicians to reduce the harmful effects on the brain.