Objective To compare the effects of medroxyprogesterone acetate (MPA) and compound norethisterone enanthate (CNE) on the susceptibility of BABL/c mice to lower reproductive tract infection withchlamydia trachomatis(Ct). Methods A total of 60 BALB/c mice were randomly and equally divided into 6 groups: MPA-pretreated control group and CNE-pretreated control group inoculated with MyCoy cell suspensions in the vagina on the 5th day after single treatment with MPA and CNE respectively, blank control group receiving no treatment, MPA-pretreated infected group and CNE-pretreated infected group inoculated with 1×107 inclusion-forming units (IFU) of Ct serovar E in the vagina on the 5th day after single treatment with MPA and CNE respectively, control infected group inoculated with the same quantity of IFU of Ct serovar E in the vagina but receiving no pretreatment. On day 4, 7 and 14 after inoculation, vaginal irrigation fluid was obtained from all the mice for cell culture of Ct. Three mice were randomly selected from each of these groups at the above three time points and sacrificed, and vaginal and uterine tissue specimens were obtained for hematoxylin-eosin (HE) staining and microscopic examination. Chi-square test and Fisher's exact test were conducted to compare infection rate among different groups. Results No growth of Ct was observed in the three control groups at the above time points. The culture-positive rate of Ct was 1/10 on day 4 but 0 on day 7 and 14 in both the CNE-pretreated infected group and control infected group, 7/10 on day 4, 2/7 on day 7 but 0 on day 14 in the MPA-pretreated infected group. Fisher's exact test revealed that the culture-positive rate of Ct was significantly higher in the MPA-pretreated infected group than in the control infected group and CNE-pretreated infected group on day 4(bothP=0.03), but similar among the three infected groups on day 7(P=0.23). Both the MPA-pretreated control group and infected group showed an increase in endovaginal mucus, thinning of vaginal stratified squamous epithelium, mucification of vaginal epithelium, presence of secretions in vaginal lumen and submucosal infiltration of a few inflammatory cells on day 4, 7 and 14, as well as appearance of pathological changes (including the presence of large quantities of purulent secretions in lumen, mild tissue edema and submucosal infiltration of a few inflammatory cells) in the vagina on day 4. Vaginal tissues were normal in both the CNE-pretreated infected group and control group at the above three time points, but mild tissue edema, lumen expansion, secretion retention and infiltration of scattered inflammatory cells were observed in the uterus on day 4 after inoculation. Conclusions MPA can arrest the estrous cycle of mice at diestrus with the mucification of vaginal epithelium, which may increase the susceptibility to Ct vaginal infection in mice. In contrast, CNE has no obvious effect on the estrous cycle and susceptibility to Ct vaginal infection despite of the appearance of pathological changes in the uterus. Key words: Medroxyprogesterone acetate; Norethindrone; Chlamydia trachomatis; Disease models, animal; Mice; Reproductive tract infections