Ration contamination with cadmium chloride (CdCl₂₎ leads to serious economic loss. The current study aimed to explain the ameliorative effect of grape seed extract (GSE) either alone or in combination with CdCl₂. One hundred and fifty chicks were used in the current study. They were equally alienated into 6 groups; group I was kept as control. Group II: given grape seed extract by the first dose (GSE1) of 250 mg/kg; group III: given grape seed extract by the second dose (GSE2) of 500 mg/kg; group IV: given cadmium chloride (CdCl₂) to evaluate the undesirable effects of the dose (100 mg/kg diet). Group V: given combination of GSE1+ CdCl₂, group VI: given combination of GSE2+ CdCl₂. At the end of the 3^rd and 5^th weeks, the following parameters were measured: Serum oxidants and antioxidants (GSH, SOD, CAT and MDA), brain oxidants and antioxidants (SOD, CAT, MDA, and NO), semi-quantitative RT-PCR detection of brain and liver GST and GPx, as well as serum cytokines (IL-1β, IL-10, and TNF-α), were determined. The results put on display show that GSE extract considerably ameliorated the levels of serum and tissue oxidants and antioxidants, as well as cytokines that ramshackle CdCl₂. Histopathological assessment of brain tissue and BAX brain sections was in concurrence with the immunological, oxidant, antioxidant, and RT-PCR results. It is important to take into consideration that the immunostimulant, antioxidative properties of GSE are mechanistically achieved. So, GSE could be used as a protective agent against ration contamination.