Objective: To observe the impact of high hydrostatic pressure on vasa vasorum in the walls of the great saphenous vein and splenic vein. Methods: The specimens of great saphenous varicose vein and portal hypertension-splenic vein (disease groups), along with the specimens of normal great saphenous vein and splenic vein (normal control groups) were collected. CD34 immunohistochemical staining and Masson staining were performed to calculate the number and cross-sectional area of the vasa vasorum in each group of vessel walls, and quantitative analysis was also conducted. Results: Morphological observation showed that there was remarkable vasa vasorum proliferation in both disease groups compared with their paired normal control groups. Quantitative analysis showed that the number and cross-sectional area of the vasa vasorum in either adventitia or tunica media in both disease groups were significantly higher than those in their paired normal control group (all P<0.05); the difference in number of the adventitial vasa vasorum between disease group and normal control group of the splenic vein was significant higher than that of the great saphenous vein, while the difference in average cross-sectional area of the adventitial vasa vasorum between disease group and normal control group of the greater saphenous vein was significantly higher than that of the splenic vein (both P<0.05), but both the differences in the tunica media between the two vessels had no statistical significance (both P>0.05). Conclusion: Under high hydrostatic pressure, the vasa vasorum is proliferated in the wall of the great saphenous vein and splenic vein, but its proliferation pattern has heterogeneity, which presented in the great saphenous vein mainly as enlargement of lumen size while in splenic vein mainly as increase of number.