Heat stress caused adverse effects which induce oxidative stress and membrane disturbances in brain. Thus, we evaluated the brain oxidative stress induced by heat stress in rabbits with consequent changes in brain neurotransmitters (adrenaline, nor adrenaline and serotonin) and examined the potential protective role of capsaicin against the changes induced by heat stress. Forty eight growing APRI rabbits were used in this study and they were divided into four groups. Rabbits were received oral doses of capsaicin dissolved in 1ml of corn oil orally three times a week for 7 weeks by using stomach tube, doses were 0 (control), 10, 30 and 50 mg/kg body weight for the four groups respectively. The results indicated that heat stress induce oxidative stress in the brain leading to alterations in the neurochemistry of the brain tissue. On the other hand, heat stress significantly increased the content of lipid peroxidation and decreased the level of non-enzymatic antioxidants and activities of antioxidant enzymes; glutathione peroxidase, superoxide dismutase and catalase and capsaicin treatment significantly decreased the contents of lipid peroxidation and significantly increased glutathione and activities of antioxidant enzymes. Also brain neurotransmitters contents were decreased in control group while capsaicin increased these values in treated group. Conclusively, capsaicin administration can improve the antioxidant defense systems and brain function during summer season.