Abstract: The function of blood-brain barrier (BBB) is to protect the central nervous system (CNS) by limiting the entry of substances from peripheral circulation via tight junctions and a large number of drug efflux transporters. The major transporters mediating drugs/toxics efflux at BBB are ATP-binding cassette (ABC) transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs). ABC transporters prevent toxins accumulation in the brain by transporting toxins out of the brain or limiting the entry of toxins into the brain. However, this is also one of the reasons for the difficult entry of CNS drugs into brain and the subsequent failure in treatment. Recent studies have shown that some diseases, including CNS diseases, diabetes and liver injury, can alter the function and expression of ABC transporters at BBB, leading to altered brain distribution and increased CNS activity or neurotoxicity. The article reviewed the alterations in the function and expression of ABC transporters at BBB induced by CNS diseases, diabetes and liver injury as well as their clinical significances, so as to provide reference for the research of drug-drug interaction under various disease conditions and provide ideas for new treatment strategies.