Abstract: Background: Recently tamoxifen-loaded solid lipid nanoparticles were introduced as innovative drug delivery system for the treatment of hormone-sensitive breast cancer. An in vitro study was conducted to determine the antioxidant status induced by tamoxifen-loaded solid lipid nanoparticles in female Wistar ovariectomized rats. Materials and Methods: In this study 36 female Wistar rats between 7-8 weeks old, weighing 159.42±6.43 g were divided randomly into 6 groups of 6 rats each. The 1st group (H) served as non-ovariectomized healthy rats and the 2nd group (C) was ovariectomized as control group. The 3rd (O), 4th (T), 5th (TS) and 6th group (S) were ovariectomized and treated with olive oil, tamoxifen, tamoxifen-loaded solid lipid nanoparticles (TMX-SLN) and solid lipid nanoparticles-free drug (SLN), respectively. The groups 2-5 were treated (2 mg kg–1) for 21 consecutive days using gastric intubations. At the end of the study, the rats were sacrificed and examined for the serum oxidative stress (TAC, TOS and MDA). The endometrial tissues were also evaluated histologically for possible damage. Results: The results of the study revealed that either tamoxifen or tamoxifen-loaded SLN during 21 days resulted in increased serum total anti-oxidant and decreased serum total oxidant status insignificantly compared to healthy and non-treated ovariectomized rats. The results also showed that the lipid peroxidation was increased insignificantly in treated groups when compared to the healthy and non-treated ovariectomized rats. No structural abnormalities were observed in endometrial tissues. Conclusion: It can be concluded that the effect of tamoxifen on the oxidative stress system is not affected and its bioavailability is increased when it encapsulated in SLN.