Over the last few decades, ecotoxicological impacts of organophosphorus insecticides have been accentuated by sharp increase of their use in agriculture. In this study the effect of orally administrated Malathion on male Japanese quail was investigated. The acute oral 72-hrs LD50 of Malathion was found to be 146.06 mg/kg B. wt. Malathion was supplied at a dose of 1/20 of LD50 for eight weeks. The evaluation strategy of the current investigation used observation of clinical signs and stress related alterations which were assessed by evaluating relative organ weights; hematological; biochemical and histopathological investigations. The tendency of Malathion to accumulate in selected tissues and organs of male treated quails was evaluated by detecting its level in liver, kidney and muscle. Significant decrease in red blood cell counts RBCs, hemoglobin (Hb) and packed cell volume (PCV) of treated quails were observed in comparison to their controls. Significant alterations in total and differential leucocytes counts were also observed. Treated quails showed a significant increase in liver enzyme activities (AST, ALT and ALP) as well as in total bilirubin and glucose levels. Meanwhile, they showed significant decrease in total protein, albumin, and globulin. Regarding kidney function; serum creatinine, urea and uric acid of treated quails were significantly increased in comparison to their control. Cholesterol, triglycerides, VLDL-cholesterol and LDL-cholesterol levels of treated quails showed significant increase in comparison to their controls, while LDL-cholesterol levels showed a significant decrease. Malathion residue concentration in liver, kidney and muscle showed higher concentration in liver and kidney followed by muscles. Histopathological alterations were observed in treated quails. Safe use and all precautions should be followed during application of Malathion to minimize such undesirable effects. [Mahmoud, H. M.; Haggag, A. M. H. and El-Gebaly, H. S. Toxicological Studies of Malathion on Japanese Quail (Coturnix Japonica). Life Sci J 2012;9(3):1725-1732] (ISSN:1097-8135). http://www.lifesciencesite.com. 251