Apis cerana is the original host for N. ceranae, and the impact of Nosema ceranae infection on A. cerana is largely unknown. In this study, workers of Apis cerana cerana were inoculated with N. ceranae spores. and the effects on the microsporidian spore load, host sucrose solution consumption, midgut epithelial cell structure, and lifespan were investigated. Spore counting suggested that the spore load in the host midguts decreased from 1 to 2 days post inoculation (dpi), while it increased from 2 to 13 dpi. No statistically significant difference in workers’ sucrose solution consumption was detected between N. ceranae-inoculated and un-inoculated groups. Microscopic observation showed darkly stained microsporidia in the midgut epithelial cells of N. ceranae-inoculated workers from 7 to 10 dpi. Additionally, the boundary of N. ceranae-inoculated host epithelial cells was blurred, the nucleus had almost disappeared, and the nucleic acid substance was diffused, whereas the boundary of un-inoculated midgut epithelial cells remained intact and the darkly stained nucleus was clear. The survival rates of workers in both N. ceranae-inoculated groups and un-inoculated groups started to decrease at 5 dpi. Additionally, the survival rate of workers in N. ceranae-inoculated groups was nearly always lower than that in un-inoculated groups, and there was a significant difference between these two groups from 11 to 20 dpi. These results demonstrate that the spore load of N. ceranae continuously elevated with microsporidian proliferation, causing damage to the midgut epithelial cell structure and shortening the host’s lifespan. Our findings offer a solid basis for exploring the molecular mechanism underlying N. ceranae infection and N. ceranae–A. cerana interaction.