To evaluate the antithrombosis of recombinant hirudin variant III emulsive microparticles (rHVIII EP) and disclose its mechanism via oral administration. Normal and DIC (disseminated intravascular coagulation) rats as well as IVC (inferior caval vein) thrombosis rats were used to determinate the pharmacodynamics of rHVIII. rHVIII was labeled with FITC (fluorescein isothiocyanate) to test the absorption of emulsive microparticles using Caco-2 monolayer model and everted gut sacs model. rHVIII EP was able to prolong thrombin time, clotting time and inhibit thrombus formation in vivo. rHVIII EP could be absorbed in the whole intestinal sections. Transport experiment indicated that the P app value was (2.68 ± 0.14) ×10 -6 cm·s −1 from AP side to BL side, and (3.02 ± 0.66) ×10 -6 cm·s −1 from BL side to AP side, respectively, indicating that rHVIII is absorbed in the intestine through passive transport. Compared with intravenous route, the absolute bioavailability of rHVIII EP via oral route was 11.42%. rHVIII EP has anti-thrombosis and anticoagulation effects with proper bioavailability. Our study here elucidated for the first time that rHVIII EP delivered via oral route has potentiality in development.