Doxorubicin (DOX) is a chemotherapeutic agent; it is widely used in human malignancies. Its long-term use can cause neurobiological side-effects. Vitamin E and Coenzyme Q10may possess neuroprotective effects. This work was designed to investigate the effect of vitamin E and the coenzyme Q10(CoQ10) supplementation on neurotoxicity induced by doxorubicin(DOX) in rats. Forty nine adult rats of both sexes were used in this study; the animals were randomly enrolled into seven groups of 7 rats each. Group I: negative control (rats administered corn oil); Group II: Vitamin E at a dose of 100mg/kg/d for 3 weeks ; Group III: CoQ10 at a dose of 50 mg/kg/d for 3 weeks; Group IV: positive control (Doxorubicin 2.5 mg/kg)every other day for 2 weeks; Group V: vitamin E at a dose of 100mg/kg/d for 3 weeks administered prior to Doxorubicin at dose2.5 mg/kg every other day for 2 weeks; Group VI: CoQ10 at a dose of 50 mg/kg/d for 3 weeks administered prior to Doxorubicin at dose 2.5 mg/kg every other day for 2 weeks. Group VII: CoQ10 (50mg/kg/day), Vitamin E (100mg/kg) for 3 weeks administered prior to Doxorubicin at dose 2.5mg/kg every other day for 2 weeks. On day twenty two of the study, brain of each animal was excised and part of it to be utilized to prepare homogenate for estimation interleukin-1 beta (IL-1β),andinterleukin-10 (IL-10); the other part of brain was used for histological examination. Vitamin E and CoQ10significantly (P<0.05) decreased IL-1beta, and only combination vitamin E and CoQ10significantly (P<0.05) increased IL-10 and there was an improvement in the histopathological lesions of the brain in group V, group VI and group VII compared to group IV. In conclusion both Vitamin E and CoQ10 may have protective effect against DOX-induced neurotoxicity in rats.