Schistosomiasis remains the second most prevalent zoonotic disease after malaria in veterinary medicine. The egg lodgement in target host tissue plays important roles in pathogenesis of this disease, but the process prior to egg-laying is still elusive. Surely, investigation of how this parasite invades and moves inside corresponding host will probably improve our understanding of homeostasis and maintenance of animal health, further, of related pathogenesis and thus potential intervention against schistosomiasis. TNT-coupled transcription/translation-expressed Sj serpin was employed for the protease inhibition assay. Transendothelial resistance (TER), its charge selectivity and size selectivity, were measured by the ussing chamber technique in serpin-transfected or recombinant serpin-treated HUVEC monolayer. The expressions of junction proteins were assayed using real-time PCR, Western blot and immunostaining. Sj serpin blocks the protease activity of elastase in a time-dependent manner; and Sj serpin can increase TER ofendothelial monolayer by decreasing its paracellular size selectivity, but not by interfere with the charge selectivity. Altered expression of tight junction protein claudin-2 was not observed at either RNA or protein levels; however, we found a marked increase in the expression of occludin, ZO-1,VE-cadherin and beta-catenin. Sj serpin can increase the transendothelial barrier function by decreasing the transendothelial permeability, implying serpin as a potential target to limit the invasion of schistosome into animal blood vessel.