Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, induces neuronal death, decreases neurogenesis, and impairs synaptic plasticity and memory, but the mechanisms for these effects are not well understood. We hypothesize that neurotrophin levels in the brain are influenced by LPS. To test this hypothesis, we determined effects of LPS on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and NT-3 levels in the brain after intraperitoneal injection of saline or LPS (0.1, 0.3 or 1.0mg/kg) in rats. LPS significantly decreased BDNF in the hippocampus (-20%), frontal cortex (-19%), parietal cortex (-63%), temporal cortex (-29%), and occipital cortex (-41%). LPS also significantly decreased NGF levels by 10-20% in the hippocampus and different cortical regions, except in the occipital cortex. Finally, LPS decreased NT-3 by 15-25% in the frontal cortex. These observations indicate that the neuroprotection mediated by neurotrophins in the brain are compromised by systemic immune activation induced by LPS.