Abstract Background: To ascertain the estrogenic effect of Zhuang Medicated Thread Moxibustion (ZMTM) and explore its time-sensitive impact on estradiol in female perimenopausal rats. Methods: Female rats were randomized into four groups of 10 rats, each consisting of the control, model, ZMTM, and acupuncture groups. The perimenopausal syndrome was induced in the last three groups with a daily subcutaneous dose of 80 mg/kg of 4- vinylcyclohexene diepoxide for 15 days. Afterward, rats in the model and control groups were fed routinely, while rats in the ZMTM and acupuncture groups were treated with six ZMTM and acupuncture courses, respectively. The rats’ general condition and estradiol (E2) levels in the rats’ serum were assessed. Results: Following the six courses of treatment, the E2 level in the model group was significantly the lowest, while the regular group was the highest (P < 0.05). There was also a gradual increase in the E2 level of the ZMTM group compared to the model and acupuncture groups, such that after the 5th and 6th courses of treatment, their E2 level was significantly higher than the model and acupuncture groups (P < 0.05). The control group had a better condition than all other groups, while the ZMTM group was better than the model and acupuncture groups. Conclusion: ZMTM can improve perimenopausal induced rats’ estrogen level, and this effect becomes better with each further treatment course.