Objective To establish the common iliac vein stenosis model in miniature pigs. Next, to observe the influence and evaluate the safety of simulated drug?coated balloons (DCB) on the stenosis segment of the common iliac vein. Methods Twenty young and healthy male miniature pigs were selected for intravenous general anesthesia. Under anesthesia, the animal model was established by oversized balloon dilatation. After the animal model was successfully established, the miniature pigs were randomly divided into an experimental group and control group. Stenosis segment veins in miniature pigs of the experimental group were occluded by two balloons and perfused with paclitaxel. These steps were not performed in miniature pigs from the control group. Venous blood specimens were taken before and two weeks after operation. Venography was performed and pathological sections of stenotic segment veins observed before and two months after the operation. Hepatorenal function index, diameter of the common iliac vein, and histological changes of the venous wall were compared between both groups. Results Seventeen miniature pigs survived to the end of the experiment. Two weeks after the operation, there were no significant differences ( P > 0.05) between the experimental group ( n = 9) and control group ( n = 8) regarding alanine aminotransferase, aspartate aminotransferase, creatine, and blood urea nitrogen values. However, two months after the operation, lumen diameter was significantly different ( P < 0.05) between the experimental group [(3.74 ± 1.24) mm] and control group [(2.25 ± 1.41) mm]. Compared with the untreated contralateral common iliac vein, the intima and media of the target vein were thicker in both the experimental group and control group. Indeed, this was more obvious in the control group than experimental group. Conclusions The common iliac vein stenosis model can be established in miniature pigs by oversized balloon dilatation. Local perfusion with paclitaxel has little effect on hepatorenal function of miniature pigs. Using this approach, simulated DCB can reduce the degree of common iliac vein stenosis in miniature pigs.