Venous thromboembolism (VTE) refers to deep venous thrombosis (DVT) and pulmonary embolism (PE), which is a worldwide problem and has very high morbidity and mortality. The research of venous thrombosis involves pathogenesis, pathophysiology, and therapeutic attempt. Alternative experimental animal models have changed dramatically over the past 20 years, from small murine models to large ones. Larger animal models offer more options and are more consistent with human physiology. This article aims to induce chronic deep venous thrombosis in the left iliac vein in canine and porcine models and compare these two models. We think that feasible large animal models can better translate the results of therapeutic research into clinical application.