Human trichinellosis is a serious disease with no effective treatment till now. Recently, the protective immunity induced by parasite-derived extracellular vesicles (EVs) are studied for some parasites such as Echinostoma caproni. The current study aimed to investigate the novel T. spiralis-derived EVs as a potential vaccine candidate for the first time in a mouse model. T. spiralis EVs were isolated and identified using transmission electron microscopy, gel electrophoresis, protein content measurements and beads-based flow cytometry. Vaccination was done by subcutaneous injection of two doses of 3.5 μg T. spiralis- derived EVs. We observed a significant reduction in T. spiralis adult worm and muscle larval counts in mice immunized with T. spiralis-derived EVs (EVs-Ts group) and controlled inflammatory changes in the intestine and muscles. The EVs-Ts group showed a higher level of IFN- γ whereas the IL-4 secretion was elevated more in the EVs group (EVs group) and showed a lower level after challenge with T. spiralis infection (EVs-Ts group). This implies a mixed Th1/Th2 immune response with obvious Th1 polarization. Moreover, elevation of serum T. spiralis-specific IgG was reported. In conclusion, this preliminary study provides T. spiralis EVs as a promising candidate for future development of anti-Trichinella vaccine.