Schistosomiasis is an endemic parasite disease and praziquantel is the only drug currently in use to control this disease. Experimental and epidemiological evidence strongly suggests that
Microtus fortis
(Mf) is a naturally resistant vertebrate host of
Schistosoma japonicum. In the present study, we found that Mf serum albumin (
Mf-albumin) and the conditioned medium of pcDNA3.1-
Mf-albumin caused 46.2% and 38.7% schistosomula death rates in 96 h, respectively, which were significantly higher than that of the negative control (p < 0.05). We also found that mice injected with
Mf-albumin had a 43.5% reduction in worm burden and a 48.1% reduction in liver eggs per gram (p < 0.05) in comparison to the control animals. To characterise the mechanisms involved in clearance, schistosomula were incubated with fluorescein isothiocyanate-labelled
Mf-albumin and fluorescent enrichment effects were found in the gut lumen of schistosomula after 48 h of incubation. Next, digestive tract excretions from schistosomula were collected and the sensitivity of
Mf-albumin to digestive tract excretions was evaluated. The results indicated that schistosomula digestive tract excretions showed indigestibility of
Mf-albumin. The death of schistosomula could be partially attributed to the lack of digestion of
Mf-albumin by digestive tract excretions during the development of the schistosomula stage. Therefore, these data indicate the potential of
Mf-albumin as one of the major selective forces for schistosomiasis.