Abstract: Blood-testis barrier (BTB) is one of the strongest blood-tissue barriers in mammals, and its special structure allows it to prevent sperms from autoimmune reactions as antigens and prevent harmful substances from entering the seminiferous tubules. The stable spermatogenic environment created by BTB is essential for maintaining male reproductive function. Research on BTB is a hot frontier in the field of male reproductive toxicology. Focusing on chemicals that can cause BTB injury and their mechanisms of action is of great significance for studying male reproductive damage induced by exogenous chemicals, and can provide a theoretical basis for the prevention of male reproductive damage caused by exogenous chemicals and the research and development of new contraceptives. This article introduced the structure and physiological function of BTB and its dynamic changes in maintaining stable internal environment during spermatogenesis, reviewed the chemicals that can cause BTB injury and their toxic characteristics, and summarized the possible mechanisms of action of BTB injury caused by chemicals. Based on the above information, the deficiencies in existing studies and the prospects for future research were put forward, aiming to provide scientific theoretical foundations and more pioneering ideas for subsequent research.