The high prevalence of sepsis in intensive care units and emergency rooms, along with the high lethality of the sepsis cases makes the study of pathophysiology of sepsis critically important. As a preclinical model, endotoxemia is an important tool to study the pathophysiology of sepsis and septic shock. In this review, we discussed aspects of endotoxemia as an experimental model in sepsis research, including different techniques associated with the purification of the endotoxin of Escherichia coli, serotype dependency and dosage dependency of the experimental results.