Vascular endothelial growth factor (VEGF) is a molecule implicated in the pathogenesis of several eye diseases. In this experimental study, we planned to evaluate the effects of surgical menopause and hormone replacement therapy on VEGF levels. Thus, we studied the effects of treatments involving estrogen, estrogen and progesterone (E/P) in combination, and genistein, which is a selective estrogen modulator, on serum VEGF levels and the expression of VEGF in the retinas of rats with surgical menopause. The rats were randomly divided into five groups. Bilateral ovariectomy (OVX) was performed in all groups except for the sham-operated group. estrogen, E/P, genistein or water (sham and control groups) treatments were given for 8 weeks through the orogastric catheter. Serum VEGF level and immunohistochemical staining of VEGF in retinal tissue were analyzed in each group. Serum VEGF levels were significantly higher in the OVX + estrogen and OVX + genistein groups than in the control and sham groups. It was also higher in the OVX + E/P group than in the sham and control groups; however, in this case, the difference was not statistically significant. The OVX + estrogen, OVX + E/P, and OVX + genistein groups exhibited increased VEGF staining in comparison with the control and sham groups. However, the difference was not statistically significant. The current study demonstrated that estrogen replacement treatment (ERT) leads to an increase in serum VEGF levels and progesterone plays a protective role in this increase. The ERT used in this study had no effect on VEGF expression in the retina.