Abstract: Macrolides antibiotics are the first choice for children infected by Mycoplasma pneumoniae（MP）which is a common pathogen of community acquired infections,as well as hospital acquired infections.Drug resistance of MP is quite severe in China,it has an important clinical significance to investigate the drug resistance mechanism of MP.This review summarized the current status of drug resistance of MP,and introduced the research progress of drug resistance mechanism in recent years.The key mechanism of drug resistance was thought to be mutations of genes located in domain V of 23 SrRNA and protein L4 and L22.Relevant researches also focused on new mechanisms.Studies of drug resistance mechanisms will provide theoretical basis for the development of antibiotics,vaccines and targeted drugs.Clinicians should pay attention to the severe drug resistance of MP and use antibiotics properly.Meanwhile,the monitoring and management of MP drug resistance should be improved.