Inflammation appears to be one of the major sources of reactive oxygen species (ROS), and most likely plays an important role in the initiation of brain damage and further mental retardation and dementia. Clinical and experimental observations indicate that endotoxeimia may be involved in the development and prognosis of neurodegenerative disorders including Alzheimer disease (AD). We have determined the electron microscopic characteristics of the brain tissue after the acute endotoxin injection. Acute experimental endotoxeimia was induced by intravenous injection nonpurified LPS from E. coli (serotype 0111:B4). Adult male white rats were treated intravenously with either LPS (1.0 mg/kg) or 0.9% sterile saline alone. 2 hr after the injection under deep anesthesia, the brains were removed and harvested into the Karnowsky's fixative and 0.1% picric acid in PBS for at least 4 hours and then processed using standard EM. Randomly selected ultrathin sections from the brain cortex and hippocampus were examined by using TEM (Jeol 1200CX). Images were captured using a digital imaging system. Endotoxin received animal brain microvessels were characterized by a sharp contraction of the endothelium and the presence of a myelin-like structure on their luminal plasmalemma. Very often, the presence of a cluster of adhered platelets, monocytes/neutrophils and erythrocytes appeared to be a permanent feature of these microvessels. Furhtermore, the tight junction between the endothelium almost disappeared. The presence of a vesicular structures in the endothelial cytoplasmic matrix also appeared to be another features of these microvessels. Moreover, perivascular regions showed edema which indicated a disruption of the blood brain barrier. The same pattern of the pathology features were also seen in glial cells and hippocampal and cortical neurons, and edematous changes and destruction of neuronal mitochondria appeared to be a hallmark of the brain tissue. Further examination of ultrastructural degeneration caused by acute and/or chronic endotoxeimia will likely contribute to our understanding of the neurodegenerative etiology caused by brain inflamation. It will also create a new avenue for the development of novel prophylactic treatment strategies by using selective anti-inflamatory medications in combination with mitochondrial antioxidants for the demented patients.