The Khat, Catha edulis (Celastraceae) chewing resulted in many diseases and physiological alterations affecting man. This fact has been observed in several previous studies. The present work was evaluated for the first time to investigate the in vivo and in vitro mode of Khat action and how it causing the etiology of diseases. Thirty healthy male rabbits weighting 1600-1800gm. were divided into 3 groups with 10 animals in each, first group served as control animals; they received orally 10 ml. of normal saline daily period of 30 day, while animals in second and third groups received a single orally dose 5g/kg and 10g/kg respectively, of powdered khat leaves, dissolved in distilled water, period of 30 days. The level of lipid peroxidation (LPO) and Methylglyoxal (MG) in liver homogenate were measured, and the levels of hydroxyl and superoxide radicals' generation in the in vitro reactions with presence of khat were also measured. Results showed a dose dependent high significant (P<0.01) increase in the level of (LPO), (MG) in liver homogenate of animals treated with Khat as compared to control animals. Results of in vitro reactions showed increase in the superoxide and hydroxyl radicals' generation.