OBJECTIVE: Quercetin is a flavonoid compound extracted from fruits and plants and is used as a natural antioxidant to prevent or treat a variety of diseases such as cancer, obesity, chronic inflammation, and reproductive system dysfunction. The aim of this study was to investigate the effects of quercetin on obesity and ovarian tissue by analyzing the expression of genes involved in the hypothalamus-pituitary-gonadal axis, including ob-Rb, ob-Ra, and brain-derived neurotrophic factor (Bdnf), neuropeptide Y (NPY), and Kisspeptin (Kiss-1). METHODS: In this experimental study, female rats were divided into three groups, and the effect of quercetin with doses of 50 and 100 mg/kg on weight and BMI was investigated. Also, the gene expression was assessed using the real-time PCR technique. The estrogen, progesterone, FSH, and LH were assessed using the chemiluminescence technique. The diameter and number of different types of follicles, corpus luteum, and blood vessels in mice were investigated. The growth indicators of the children, including the number, weight, and height and head width of the born children, were checked. RESULTS: Quercetin caused a decrease in BMI, a significant increase in the expression of ob-Rb, ob-Ra, and Bdnf genes, a significant decrease in the expression of NPY and Kiss-1 genes, and led to an increase in sex hormones. Quercetin improved follicular indices and increased the number of mouse embryos. CONCLUSIONS: Probably, quercetin affects the hypothalamus-pituitary-gonadal axis by changing the expression of genes, and it helps to reduce obesity and increase fertility and better function of the reproductive system.