Cephalosporin is still the first-line drug chosen for the treatment of gonorrhea, although it is likely to develop resistance to Neisseria gonorrhoeae. Recently, the resistance or low sensitivity of cephalosporin to Neisseria gonorrhoeae have been reported at home and abroad. The studies of resistance mechanism to Neisseria gonorrhoeae are particularly important. The resistance mechanism is mainly lied in three aspects. The first is the changes in antibiotic target sites, for example, the changes in penicillin-binding proteins would affect the binding of antibiotics to Neisseria gonorrhoeae; the second is the changes in bacterial cell membrane porin which effects drugs influxing; the third is the changes in efflux system which enhances the bacterial efflux capacity. To study and explore the mechanism of Neisseria gonorrhoeae resistance is of great importance for the prevention and treatment of gonorrhea.