Introduction: Toluene is an organic solvent widely used in many industrial processes and the central nervous system is a primary target in both acute and chronic exposure to toluene toxicity. Vitex agnus castus (VAC) fruit is a source of phytoestrogens, flavonoids, and apigenin, and has a great antioxidant ability. The purpose of this study was to evaluate the protective effect of VAC fruit on toluene-induced lipid peroxidation in mice brains. Method & Materials: In the experimental study, 50 male mice (25-35 g) were divided into five groups: control, vehicle, VAC fruit extract, toluene, and toluene plus VAC fruit extract (100 mg/kg). Toluene and the extract were injected intraperitoneally for 14 consecutive days. In the toluene plus VAC fruit extract group, first, toluene was injected and after 2 hours the extract was injected. After 14 days, the hippocampal area was extracted and lipid peroxidation was evaluated by measuring the MDA level. Results: Toluene caused a significant increase (P < 0.001) in MDA level compared to the control group. Whereas treatment with the VAC fruit extract caused a significant decrease (P < 0.001) MDA level compared to the toluene group. Discussion: Our result showed that VAC fruit treatment significantly increases toluene-induced lipid peroxidation may be via antioxidant activity. Therefore, the neuroprotective effects of VAC fruit can be useful in medicine.