Investigating the therapeutic effect of genistein (Gen) on postmenopausal senile vaginitis (SV) and its mechanism of action. Adult SPF female Wistar rats were selected to establish a bilateral ovariectomized animal model (OVX), which simulated senile vaginitis dominated by estrogen deficiency in ovarian dysfunction. After 14 days of continuous treatment, the morphology of vaginal epithelial tissue was observed and various types of epithelial cells were counted, and the body mass and uterine and vaginal index of rats were measured. the levels of vaginal tissue secretion, microorganism, hormone and glycogen in each group were measured and the reproductive health was evaluated clinically. The protein expression and mRNA expression of epidermal growth factor (EGF) and E-cadherin (E-cadherin) in vaginal tissues were detected by immunohistochemistry and RT-PCR, respectively. Result showed that Genistein lowered vaginal pH, increased vaginal index and vaginal health score, thickened epithelial layers and improved vaginal tissue atrophy after administration. Genistein also increased the contents of glycogen and Lactobacillus in vagina, and promoted the expression of EGF, E-cadherin protein and mRNA. To sum up, there is no significant change in serum E2 and FSH levels, indicating that genistein has no effect on hormone levels in rats. genistein promoted the proliferation of vaginal epithelial cells, thickened epithelial layers and the vaginal wall, which improved the resistance of vaginal epithelium, the recovery of self-cleaning ability and healed the vaginal wound and erosive surface to improve atrophy.