Objective: To describe the state of the art on the role of the toll-like receptor 4 in the pathogenesis of periapical lesions in experimental models. Methods: A systematic search procedure was carried out to reach the available literature on the subject in databases and specialized scientific journals: MEDLINE, Embase, Web of Science, Google Scholar, International Endodontic Journal, Journal of Endodontics and Australian Endodontic Journal. Results: Four studies were included in the scope of the review. From an operational point of view, all studies induced the formation of periapical lesions by contamination of root canals. The experimental models were rats and mice, including animals that were wild-type or that had mutation or knockout in Tlr4 gene. In general terms, TLR4 signaling was associated with inflammation and resorption of periapical tissue in wild-type mice and rats. The expression of this receptor tends to increase along the pathogenesis of periapical lesions. In TLR4-deficient mice, controversial outcomes have been observed. In a lipopolysaccharide hyporesponsive model due to Tlr4 mutation, there is evidence of reduced periapical bone resorption. However, one study did not observe these differences. Current studies have significant limitations to consolidate these outcomes, including the number of animals in the experiments, statistical analyzes and experimental periods used. Conclusion: It is possible to conclude that TLR4 may act significantly in the genesis and development of periapical lesions in experimental models.