BACKGROUND: Stellate ganglion block has the ability to improve the imbalance of the autonomic nervous system in perimenopausal syndrome. Lumbosacral plexus is an automatic nervous block, and exerts similar effects with stellate ganglion block. OBJECTIVE: To investigate the effect of lumbosacral plexus block on the serum level of hormones and histology of the ovary in rabbits, thus providing a new treatment strategy for perimenopausal syndrome. METHODS: This was a randomized controlled animal experiment, which was finished at the Animal Center of Guiyang Medical Unversity, China. The healthy rabbits were randomly divided into experimental and control groups, and underwent lumbosacral plexus block by injecting 0.5 mg of vitamin B12, 100 mg of lidocaine and 10 mL of normal saline into the psoas compartment, and the same volume of normal saline, respectively. The effect of lumbosacral plexus block on the serum levels of hormones (estradiol, gonadotropin releasing hormone, follicle-stimulating hormone and luteinizing hormone) at rabbit proestrus, estrus and metaestrus were observed, respectively. The pathological changes of the ovary in a complete estrus cycle were observed. The relationship between the treatment time of lumbosacral plexus block and the levels of hormones was investigated after 1, 3 and 6 complete estrus cycles. The experimental followed the national guidelines for the Care and Use of Laboratory Animals, and Consensus author guidelines on animal ethics and welfare by the International Association for Veterinary Editors (IAVE), and prepared in accordance with the Animal Research: Reporting of In Vivo Experiments Guidelines (ARRIVE Guidelines). RESULTS AND CONCLUSION: Lumbosacral plexus block can increase the serum level of estrogen, reduce the serum levels of follicle-stimulating hormone and luteinizing hormone, and regulate the hypothalamic-pituitary-ovary axis function. Presumably, it may be used as a treatment method or adjuvant therapy of perimenopausal syndrome. Future experiments are needed to explore the effect of lumbosacral plexus block on the serum levels of hormones in a rabbit after oophorectomy to determine whether it exhibits the same effect on ovarian failure.