Objective: To investigate the changes in apoptosis of cells in different venous walls under high hydrostatic pressure and the mechanisms. Methods: Samples of portal hypertension induced diseased splenic veins (DSV) and varicose great saphenous veins (VGSV) were collected, and samples of normal splenic veins (SV) and great saphenous veins (GSV) were used as control. The apoptotic cells in the venous walls were detected by TUNEL assay and immunofluorescence staining, the apoptosis-related protein Bax and Bcl-xl expressions were determined by immunohistochemical staining, and the cell ultrastructural changes were observed with an electron microscope. Results: In the wall (intima and media) of the DSV and VGSV compared with respective control, the apoptotic ratio was significantly reduced (both P<0.05); the proapoptotic protein Bax expression was reduced, antipoptotic protein Bcl-xl was elevated and Bax/Bcl-xl ratio was significantly decreased (all P<0.05). The endothelial and smooth muscle cells in the walls of DSV and VGSV exhibited fuzzy mitochondrial cristae, medullary changes, and margination of the nuclear chromatin. Conclusion: Under high hydrostatic pressure, there is a similar dysregulation in mitochondrial pathway of apoptosis in different venous walls, which is probably an important mechanism for venous wall dilation and thickness in relevant disease conditions.