High-fat diet (HFD) contributes to neuroinflammation forming, hence it is crucial to find safe and effective substances that are able to counteract its progress. The anti-inflammatory properties of phytocannabinoids acquired from the Cannabis plant have been widely acknowledged. We evaluated the effects of cannabidiol (CBD) treatment on induced by applying HFD early stages of neuroinflammation in Wistar rat cerebral cortex. In our 7-week experiment, CBD was injected intraperitoneally over the last 14days at a dose of 10 mg/kg of body weight once a day. The level of arachidonic acid, a precursor to pro-inflammatory eicosanoids, decreased in all analysed lipid classes after CBD administration to the HFD group. Moreover, the extent of diminishing the activity of the omega-6 (n-6) fatty acid pathway by CBD was the greatest in diacylglycerols and phospholipids. Surprisingly, CBD was also capable of downregulating the activity of the omega-3 (n-3) pathway. The expression of enzymes involved in the synthesis of the eicosanoids was significantly increased in the HFD group and subsequently lowered by CBD. Significant changes in various cytokines levels were also discovered. Our results strongly suggest the ability of CBD to reduce the formation of lipid inflammation precursors in rat cerebral cortex, as a primary event in the development of neurodegenerative diseases. This can raise hopes for the future use of this cannabinoid for therapeutic purposes since it is a substance lacking lasting and severe side effects.