HIS STUDY was carried out through 2010-2014, seasons on on …fresh herbs of Plantago major plant, which was collected from a private nurseries of El Qanater el Khayreyya, Al-Qaluobia Governorate, Egypt. The aim of this study was to investigate the protective potential of ethanolic crud extract of Plantago major against oxidative stress induced by carbon tetrachloride (CCl 4) in different tissues in rats. Our results observed that CCl4 exhibited a significant increase in the levels of serum glucose and lipid profile i.e. total cholesterol, triglyceride and low density lipoprotein cholesterol (LDL) with a significant decrease in the level of high density lipoprotein cholesterol (HDL). Also, CCl4 increase liver function including serum aminotransferases (AST and ALT), alkaline phosphatase (ALPh), total protein, albumin (ALB) and total bilirubin activities and kidney function including the levels of serum urea, uric acid and creatinine amounts. Treatment with ethanolic P. major extract at 100mg/kg b.wt before, with and after treatment with CCl4 significantly prevented all of these typically observed changes. Also, P. major extract statistically significant (P<0.01) inhibit DNA damage induced by CCl4 in bone marrow and sperms of rats. Our findings indicate that P. major has a significant protective effect against CCl4 induced genotoxicity and biochemical changes in rat, which may be due to its antioxidant properties.