〔Abstract〕 Objective To establish a castrated male mouse model and to preliminarily investigate the effects of tes_ tosterone replacement therapy（TRT）on behavior ，serum indices ，and histopathological changes in castrated mice，as well as to explore the role of androgens in cognitive function. Methods Forty 6-month-old male C57/ BL6J mice were randomly divided into sham operation group，castration group，testosterone propionate（0. 5 mg/ kg）treated group，and testosterone propionate（1. 0 mg/kg）treated group，with 10 mice in each group. Following castration and subcutaneous administration of testosterone propionate at different doses（0. 5 and 1. 0 mg/kg）for TRT，learning and memory abilities were assessed using the Morris water maze（MWM）test and the passive avoid_ ance test. Serum testosterone and serum brain-derived neurotrophic factor（BDNF）levels were measured by ELISA，and histopathological changes in the hippocampus were examined using hematoxylin-eosin（HE）staining. Results Routine observations：there were no statistically significant differences in body weight among groups at any time point. MWM test：compared with castration group，sham operation group and testosterone propionate- treated groups（0. 5，1. 0 mg/kg）showed significantly reduced escape latency on days 4 and 5（P<0. 05），while the number of platform crossings and the time spent in the target quadrant significantly increased（P<0. 05）. Pas_ sive avoidance test：the number of passive avoidance errors significantly decreased in sham operation group and tes_ tosterone propionate（1. 0 mg/kg）-treated group（P<0. 05）， and the passive avoidance latency was significantly prolonged in sham-operated group and testosterone propionate-treated groups（0. 5，1. 0 mg/kg）（P<0. 05）. Serum testosterone and serum BDNF assays：serum testosterone levels and serum BDNF concentrations significantly in_ creased in sham operation group and testosterone propionate-treated groups（0. 5 ，1. 0 mg/kg）（P<0. 01）. HE staining：compared with sham operation group，neuronal density in all hippocampal subregions was slightly re_ duced in castration group；in the testosterone propionate（0. 5 mg/kg）-treated group，neuronal arrangement in the CA 1 and CA3 regions was improved and apoptotic cells were reduced compared with castration group；in testoster_ one propionate（1. 0 mg/kg）-treated group，the pyramidal cell layer in the CA3 region was more compactly ar_ ranged，with fewer apoptotic cells than in castration group. Conclusion TRT improves learning and memory per_ formance in castration male mice，potentially through modulation of hippocampal BDNF signaling pathways.