Cervicitis is a clinical syndrome characterized by inflammation of primarily the columnar epithelium of the uterine endocervix. It can be acute or chronic. Prostaglandin endo peroxide synthase2 (Cyclooxygenase-2) is a key enzyme in prostaglandin synthesis, which is coded by the PTGS2 gene, and recognized as the master switch that activates the inflammatory response; its induction leads to the biosynthesis of prostaglandins. The current study aims to determine the CA125, CA 19.9, and, CA 15.3 markers level and their relationship with the COX-2 gene. Venous blood samples were obtained from 100 women with cervicitis whose ages ranged from 18 to 60 years, and 100 healthy women as a control group. Detection of CA19-9, CA- 125 and CA 15-3 markers was performed by using Cobas E411 analyzer while the CRP test was detected by using Afias CRP instrument. The conventional PCR was used for gene detection and DNA sequencing. The mean± SD of Ca125, CA15.3 and CRP showed a highly significant differences between patient (30.33±1.09), (22.82±1.07), (88.06±5.88) respectively and the healthy control (19.40±0.68), (18.34±0.77), (6.73±0.12) respectively-value >0.001. The mutation in PTGS2 gene with highly CA125 marker 100(100%) and CRP levels 20(80%), while in CA15.3 marker 3(15%) and CA19.9 marker 1(5%). The mutation occurrence in analysis of rs20417 NSP of PTGS2 gene with wild CC GG and the variation C>G G>C.