The present study was designed to investigate the possible protective effect of vitamin E against some adverse effects of levofloxacin in male rats. This experiment was done on twenty five male rats, four months old apparently healthy weighing 200±10g, divided randomly into 5 equal groups (5 rats in each). 1st group rats received 0.2ml/kg b.wt. distalled water orally (control group), 2nd group rats received 0.2ml/kg b.wt. olive oil orally. 3rd group rats received vitamin E 100mg/kg b.wt. orally. 4th group rats received levofloxacin 10mg/kg b.wt. orally. 5th group rats received vitamin E 100mg/kg b.wt. orally and levofloxacin 10mg/kg b.wt. orally. Treatment duration was 14 successive days for all groups. Levofloxacin evoked a significant decrease in total erythrocytic count, hemoglobin content (Hb), packed cell volume percent (PCV), platelets count (PLT), total leukocytic count (TLC), differential leukocytic count (lymphocytes, neutrophils and monocytes), high density lipoprotein (HDL), superoxide dismutase (SOD) and catalase (CAT) levels beside an elevation in liver enzymes activities (AST, ALT, ALP), total cholesterol (TC) , triglycerides (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), urea level, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) level coupled with non-significant effect on MCV, MCHC, serum total protein, albumin, globulin levels, A/G ratio and serum creatinine level. Concurrent administration of vitamin E with levofloxacin produced a significant increase in total erythrocytic count, (Hb), (PCV), (PLT), (TLC), differential leukocytic count (lymphocytes, neutrophils and monocytes), (HDL), (SOD) and (CAT) levels coupled with a significant decrease in liver enzymes activities (AST, ALT, ALP), (TC), (TG), (LDL), (VLDL), urea level, MDA, TNF-α level beside non-significant variations of  MCV, MCHC, serum total protein, albumin, globulin levels, A/G ratio and serum creatinine level. In the light of the present investigation it could be concluded that administration of levofloxacin induced adverse effects in blood picture, liver enzymes, protein profile and oxidant/antioxidant status. Vitamin E induced ameliorations in some adverse effects of levofloxacin via its antioxidant effect.