Schistosomiasis remains a serious public health concern in China.BALB/c mice are susceptible to Schistosomajaponicum infection,whereas the Wistar rats are less susceptible to this parasite.In the current study,apoptosis was observed in 14 d,23 d,32 d,and 42 d worms of S.japonicum from both rats and mice at the morphologic,cellular,and gene levels by transmission electron microscopy(TEM),fluorescein isothiocyanate-annexin-Ⅴ/propidium iodide staining,flow cytometry analysis and real-time PCR.Several classical hallmarks of apoptosis,including cell shrinkage,chromatin condensation and lunate marginalization,splitting of the nucleoli,nuclear shrinkage,and apoptotic bodies,were observed by TEM in all worms.Statistical analysis revealed that the degree of apoptosis and percentage of necrotic cells in worms from Wistar rats among all four developmental stages were significantly greater(p < 0.01)than those from BALB/c mice,except there were differences in the percentage of early apoptotic cells from 23 d worms,and an increasing difference was observed in the 32 d and 42 d worms by flow cytometry.A total of 15 apoptosis-associated genes were identified from S.japonicum in this study.Real-time PCR analyses revealed that each of the tested apoptosis-associated genes were expressed in all four developmental stages of S.japonicum,and fewer gene expression differences were observed in 14 d juvenile schistosomula.However,expression levels of most of the genes,except CASP7,were significantly higher or at the similar level in 32 d and 42 d schistosomes from Wistar rats,as compared to those from BALB/c mice,which was consistent with the observation of morphology and flow cytometry.The results obtained in this study collectively demonstrated that differential development of S.japonicum in non-susceptible rats and susceptible mice was significantly associated with apoptosis in the worm,and provide valuable information to guide further investigations of the mechanisms governing apoptosis and host-schistosome interactions.