<p>Circulating endotoxin is mainly derived from gut microbiome and is frequently increased after meals. However, the interplay between endotoxemia and innate immune cells in systemic inflammation remains unclear. The aim was to investigate the role of endotoxemia in systemic inflammation, focusing on the immune responses in innate immune cells. Menopausal women (<i>n</i> = 174) were divided into 2 groups. Blood samples were collected from the participants of group 1 (<i>n</i> = 80), who fasted for at least 8&#xa0;h, to analyze the correlation between endotoxin levels, fatty acid-binding protein 2 (FABP2), markers of systemic inflammation, and nuclear factor-κB (NF-κB) activation in leukocytes. The participants of group 2 (<i>n</i> = 94) fasted for at least 8&#xa0;h and received oral glucose tolerance test (OGTT). Their fasting and post-OGTT blood samples were also collected to evaluate the impact of postprandial endotoxemia on the expression of NF-κB target genes in leucocytes. The study revealed that circulating endotoxin level was significantly associated with FABP2 level and NF-κB activation in leukocytes after fasting and within a 2&#xa0;h-OGTT period. Variation in endotoxin levels (about 1 EU/ml) was sufficient to modulate NF-κB activation in leukocytes. These results provide clues for understanding the effects of postprandial endotoxemia on immune cell activation and inflammation induction. Our findings suggest that an increase in intestinal barrier permeability might be linked to endotoxemia-induced systemic inflammation in menopausal women.</p>