Lipopolysaccharide (LPS) as an endotoxin forms part of the cell wall of gram-negative bacteria and is responsible for initiating an acute inflammation after entering the living tissue. In this study, male rats were divided into eight groups: control group, vitamin E (VE) treatment group (200 mg/kg body weight (b.w.)), sodium selenite (SS) treatment (0.35 mg/kg b.w.) group, VE + SS treatment group (200 + 0.35 mg/kg b.w.), LPS treatment group (10 mg/kg b.w.), LPS + VE (10+200 mg/kg b.w.), LPS + SS treatment (10 + 0.35 mg/kg b.w.), and LPS + SS + VE treatment (10 + 0.35 + 200 mg/kg b.w.) group. Oxidative stress parameters, pathological changes, immunohistochemical analyses, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling (TUNEL) assay, and changes in DNA structure with comet assay of the kidney were investigated at the end 6 h comparatively with the control group. When LPS-treated group was compared with the control group, antioxidant enzyme activities were decreased and malondialdehyde (MDA) levels, changes in histological and DNA structure and apoptosis were increased significantly at the end of 6 h. However, when LPS + SS and/or VE-treated group were compared with the LPS-treated group, superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities were increased and MDA levels were decreased significantly at the end of the treatment period. Light investigations figured out pathological changes in kidneys of LPS- and LPS + SS and/or VE-treated groups. There was a decrease in the number of proliferating cell nuclear antigen-positive cells and an increase in the number of TUNEL-positive apoptotic cells in the wall of the distal and proximal tubules. As a result, it was observed that the combined use of antioxidants was more protective than their use alone against LPS.