Stress is known to produce many effects on the body as O2 free radical production, hyperglycemia, hypercholestrolemia and hyper- triglyceridemia. Melatonin is known to be a highly efficient free radical scavenger, it is also known to produce some metabolic changes, Little is known about the role of melatonin in stress. The aim of the present work was to study the effect of melatonin on stress induced O2 free radical production, hyperglycemia, hypercholestrolemia and hyper triglyceridemia. The results obtained showed that immobilization stress caused a significant increase in the plasma level of O2 free radical, as indicated by the plasma level of malondialdehyde (MDA), glucose, cholesterol and triglycerides ( P < 0.05 ). Melatonin administration prior to stress caused a significant decrease in the stress — induced O2 free radical production ( P < 0.01 ) while it has no significant effect on the stress induced hyperglycemia , hypercholestrolemia and hypertriglyceridemia. Thus, the present study might give a new meaning for the emerging role of melatonin as anti-stress hormone.