This study aimed to determine the effects of tamoxifen on sciatic nerve crush injury in a rat model using histopathological, histomorphometric, and immunohistochemical approaches. In this study, 24 male Sprague-Dawley rats aged of 5 to 7 weeks and weighing between 300 g and 400 g were used. The rats were randomly divided into 3 groups: control (group C), sciatic nerve injury (group SNI), and sciatic nerve injury with tamoxifen (group SNT). The sciatic nerve crush injury model was performed using the De Koning's crush force method. In group C, only a skin incision was made and then the skin was sutured. In group SNI, the injury model was performed but no treatment was applied. In group SNT, the injury model was executed, and then 40 mg/kg/day tamoxifen was given for 4 weeks by intraperitoneal methods. At the end of 4 weeks, all animals were killed using high doses of an anesthetic. Approximately, 2-cm sciatic nerve samples were obtained for histopathological, histomorphometric, and immunohistochemical analyses using the old skin incision. In the histopathological examination, vascular congestion and density of vacuolization were significantly lower in group SNT than in group SNI (p<0.05). In the histomorphometric examination, the mean sciatic nerve diameter was 306±62 µm in group C, 510±42 µm in group SNI, and 204±23 µm in group SNT. A significant difference was observed in the sciatic nerve diameter measurements among the 3 groups (p<0.05). In pairwise comparisons, the mean sciatic nerve diameter was significantly lower in group SNT than in group SNI (p=0.00002). Sciatic nerve diameter measurements of both groups were found to be significantly higher than group C (p<0.05). The mean epineurium thickness was 17±0.8 µm in group C, 32±2.5 µm in group SNI, and 17±0.8 µm in group SNT. A significant difference was observed in the epineurium thickness measurements among the 3 groups (p<0.05). In pairwise comparisons, the epineurium thickness was significantly higher in group SNI than in groups SNT and C (p<0.05). In the immunohistochemical analysis, S100 immunoreactivity was found significantly higher in group SNI than in the other 2 groups (p<0.05). The histomorphometric, histopathological, and immunohistochemical data obtained from this study have shown that tamoxifen has a beneficial effect on sciatic nerve crush injury in the experimental rat model.