Background: Hyperlipidemia is an important public health problem. It has been linked to numerous disorders of the neurological system. A well- Email: drsamrreda@yahoo.com known flavonoid with a variety of medicinal uses is chyrsin. Therefore, the current study objectives were to identify the effects of high fat diet (HFD)- induced hyperlipidemia on the cerebral and cerebellar cortex of adult male albino rats, and to assess the potential protective effect of chrysin. Methods: Forty five rats were divided into three groups: Control group, Hyperlipidemic group which were fed HFD for four weeks, and Hyperlipidemic+ Chrysin group which were fed HFD+ Chrysin. Results: Hyperlipidemia caused significant increase in serum cholesterol, LDL and TG, while serum HDL was significantly-decreased. There were significant increase in brain levels of TNFα, IL6, IL1, amyloid beta (Aβ), VEGF and MDA, and significant decrease in brain GSH and SOD with histological alterations in sections of the cerebrum and cerebellum. Some neurons appeared with apoptotic nuclei which characterized by neuronal shrinkage and chromatin condensation and congested blood vessels between them. Also, weak stained Nissel’s granules in the cytoplasm of neurons and cytoplasm of Purkinje cells were noticed. Hyperlipidemic group showed significant increase in area percent of GFAP and optical density of caspase 3 immunoreactions. Conclusions: Usage of chrysin ameliorated both the biochemical and the morphological changes induced by HFD administration. Chrysin is able to protect against neuronal cell damage by inhibiting oxidative stress and inflammation.