Objective: The present study aimed to contribute the ability of quercetin and /or lecithin to attenuate ifosfamide neurotoxicity. Seventy female albino rats were randomly divided into seven groups. Ifosfamide (IFO; 80mg/kg b.wt.) was administrated for five consecutive days intraperitoneally (i.p.), while quercetin (50mg/kg b.wt.) and lecithin (100mg/kg b.wt) were given orally either singly or in-combination with IFO for six consecutive days. Results: Ifosfamide induce neural toxicity as indicated by decreased GSH/GSSG ratio and elevated NO level in different brain areas. As well as altering neurotransmitters levels accompanied by inhibition of choline esterase activity in serum. Also, it stimulates an apoptotic signaling program by up-regulation of caspase-3 and assimilation of Bcl-2 gene expression in all tested brain areas. Pretreatment with quercetin and lecithin singly or incombination could attenuate ifosfamide neurotoxicity by variable degrees of improvement. This improvement seems to be a parameter selective among different brain areas. Conclusion: The present study concludes that pretreatment with combined therapy showed more pronounced effect compared to singular one. Therefore, we suggested that the synergistic effect of quercetin and lecithin in the combined treatment results in marked neuroprotective effect in part through their antioxidant properties and intervening in apoptotic pathways.