Abstract: Objective To investigate the protective effect of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes against testicular ischemia-reperfusion injury (IRI) in rats. Methods Rat BMSCs were isolated, cultured and identified in the primary culture. The exosomes were extracted from the BMSCs and characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Twenty-four healthy male SD rats were randomly divided into sham operation group, testicular IRI with saline treatment group and IRI with exosome treatment group. The contralateral testes of the rats were collected for pathological observation, aseessment of superoxide dismutase (SOD) and malondialdehyde (MDA), and detection of HMGB1, caspases-3 and cleaved caspase-3 expressions using Western blotting. Results We successfully obtained exosomes from rat BMSCs. Testicular IRI significantly impaired testicular spermatogenesis, which was markedly improved by treatment with the exosomes (P<0.05). Testicular IRI also caused significant increase in the protein expression of HMGB1, caspase-3 and cleaved caspase-3 in the testicular tissue, and treatment with the exosomes obviously ameliorated these changes (P<0.05). Conclusion BMSCs-derived exosomes protects against testicular IRI due to the anti-oxidant, antiinflammatory and anti-apoptosis activities of the exosomes.