Objective This study tried to reduce the observation time points in the establishment of a murine menstruation model, which was originally developed by Finn CA in 1984. Therefore, to make the murine menstruation model more economical and easier to handle. Methods Adult female C57BL/6 mice were ovariectomized, then sequentially treated with hormones. 4-6 hours after the last hormone injection, 0.02 ml sterilized arachis oil was injected into the uterine lumen of experimental mice. The control group only received the sham operation. Uteri were collected after oil treatment for 31-35 hours (group T3) and 56-70 hours (group T4), measuring wet uterine weight, doing H&E staining and using CAST2 image analysis software to measure the total uterine cross-sectional area (TUA) and endometrial cross-sectional area (EA). Results Through histological examination, estrogen treated group showed simple columnar epithelial cells, with high nucleus-to-cytoplasm ratio and elongate sausage-shaped nuclei with dense chromatin. After combined treatment with progesterone, secretory cells and their secretions were easily found in the glandular lumens. After oil treatment endometrium sloughing was observed in group T3, while endometrial epithelium repaired completely in group T4. Endometrium of control groups kept intact during the whole process. Wet uterine weight had no significant changes during sequential hormone treatment. After hormone withdrawal, the wet uterine weight decreased in the experimental groups slower than that of control mice. TUA and EA significantly increased after combined treatment with progesterone. 30-35 hours after oil treatment TUA increased, whereas EA did not changed. 56-70 hours later both of them decreased. Conclusion The histological changes of endometrium in this murine menstruation model displayed many features resembling human menstruation, especially, the endometrial subluminal epithelium sloughing and early endometrial repair.