OBJECTIVE In this study, potential protective effects of Bortezomib (Bort), as a proteasome inhibitor, were investigated on the uterus of ovariectomized rats by histological, morphometric and immunohistochemical methods. METHODS In this study, 18 Sprague dawley strain female rats (12 weeks old, 250-300 g body weight) were used. Animals in the control group (Cont, n=6) were not exposed to any treatment. Ovariectomy was performed on the experimental groups. They (n=12) were divided into ovariectomy (Ovt, n=6) and Bortezomib (Bort, n=6) subgroups. Twelve weeks later, the rats were perfused. Then, uterine tissues were removed and examined by morphometrical, and light and electron microscopy methods. In addition, immunoreactivity of nuclear factor-kappa (NF-κB) was evaluated. RESULTS Morphometric and histopathological evaluations showed that Bort was effective in the uterus and protects the layer structures and the cells. CONCLUSIONS In the light of these findings, we suggest that for proteasome inhibitor particularly Bort is thought to be useful through proteasome inhibition and NF-κB pathway.