The garlic has been widely used as medicinal plant for its therapeutic properties This study was aimed to investigate the antioxidant role of garlic (G) against oxidative stress induced by malathion (M) in male albino rats. After experimental period (28 days), the study investigated some biochemical parameters and oxidative stress markers in plasma rats. The results revealed that, malathion induced significant increase in plasma Tri-iodothyronine (T3), Thyroxin (T4), glucose values and malondialdehyde (MDA) as oxidative stress marker was noticed. However, significant decrease was recorded in cholesterol, total protein (T. Protein) contents and in defense system biomarker total SH- protein. Acetylcholinesterase (AChE) activity was inhibited by malathion treatment and cause alteration in non-specific esterase and protein pattern. Finally, these results concluded that garlic has significant protection against malathion intoxication demonstrated inhibition in acetyl cholinesterase (AChE) activity and reduced in cholesterol, T. protein and total SH- protein. Further studies are necessary to investigate the significant effect of garlic on thyroid gland, brain and neurotransmitters.