Acrylamide (ACR) is one of the most organic compounds which is present in many products in our life. It is one of the potential environmental health problems resulting from its increased accumulation in the process of cooking foods at high-temperature. Also, it is an industrial chemical with a wide range of uses in research laboratories, waste water treatment and cosmetic products.The aim of the study was to evaluate the toxic effect of acrylamide on the brain of adult male albino rats and the possible protective role of crocin.Forty adult male albino rats were included in the study. Rats were divided randomly into five groups (8 rats in each group);Group I: (negative control). Group II(positive control): rats received 1mldistilled water orally. Group III(crocin treated group): rats received crocin (50 mg/kg) five days per week for 12 weeks dissolved in 1ml distilled water. Group IV(ACR treated group): rats received ACR (15mg/kg) five days per week for 12 weeks dissolved in 1ml distilled water. Group V(crocin and ACRtreated group): rats received crocin in the same dose thenACRin the same dose five days per week for 12 weeks.At the end of the study, animals were subjected to estimation of acetylcholinestersae,creatine kinase BB, malondialdehyde and reduced glutathione. The cerebral cortex tissue was processed for estimation of brain derived neurotrophic factor plus histological and immunohistochemical examination.The results revealed a statistically significant decrease in acetylcholinesterase, brain derived neurotrophic factor and reduced glutathione levels in ACR group as compared to control group. Also, there was a significant increase in creatine kinase BB and malondialdehyde levels in ACR group when compared with the other groups.Histopathological examination revealed neuronal degeneration, astrogliosis, cytoplasmic vacuolations and thick meninges. Immunohistochemical examination revealed positive immunoreaction to the apoptotic marker caspase-3in the neuronal cells of ACR group when compared with the control group.Marked improvement in all these hazardous effects nearly to control values was recorded in (crocin and ACR) group.From the above mentioned results, it can be concluded thatACR induces oxidative stress, apoptosis and alterations in the neurotransmitters levels, leading to neurodegenerative disorders. Crocin can protect from these hazardous effects.