Oxidative stress has been defined as disturbance in the equilibrium status of pro-oxidant/antioxidant system in intact cells.Thus the aim of the present work was designed to study the effect of endotoxin (LPS)-induced stress on some biochemical parameters in male rats , the effect of pre-administration of thymoquinone and hesperidin as antioxidants alone and in combination in stressed rats was also concerned. The effect of LPS and its modulation by antioxidants were assessed by estimating serum corticosterone, glucose, TNF and total antioxidant capacity level, and brain MDA, ATP, ADP, cholesterol, and phospholipid contents in addition to SOD, Na+/K+ ATPase enzyme activities. Histopathological and immunohistochemical (Caspase-3, Bax, Bcl-2) examinations were also considered.