AIM: To investigate the expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) in the development of esophageal varices in portal hypertensive rats.METHODS: Thirty male Sprague-Dawley (SD) rats in the model group in which a two-stage ligation of portal vein plus ligation of the left adrenal vein was performed, were divided into three subgroups (M7, M14, and M21) in which the rats were kiued on the seventh day, the 14th d and the 21 d after the complete portal ligation. Thirty male SD rats, which underwent the sham operation in the control group, were also separated into three subgroups (C7, C14and C21) corresponding to the models. The expression of TNF-α and VEGF in the esophagus of all the six subgroups of rats were measured with immunohistochemical SP technique.RESULTS: The portal pressure in the three model subgroups was significantly higher than that in the corresponding control subgroups (23.82±1.83 vs 11.61±0.86 cmH2O,20.90±3.27 vs 11.43±1.55 cmH2O and 20.68±2.27 vs 11.87±0.79 cmH2O respectively, P＜0.01), as well as the number (9.3±1.6 vs 5.1±0.8, 11.1±0.8 vs 5.4±1.3 and 11.7±1.5 vs 5.2±1.1 respectively, P＜0.01) and the total vascular area (78 972.6±3 527.8 vs 12 993.5±4 994.8μm2, 107 207.5±4 6461.4 vs 11 862.6±5 423.2 μm2 and 110 241.4±49 262.2 vs 11 973.7±3 968.5 μm2 respectively,P＜0.01) of submucosal veins in esophagus. Compared to the corresponding controls, the expression of TNF-α and VEGF in M21 was significantly higher (2.23±0.30 vs 1.13±0.28and 1.65±0.38 vs 0.56±0.30 for TNF-α and VEGF respectively, P ＜0.01), whereas there was no difference in M7 (1.14±0.38 vs 1.06±0.27 and 0.67±0.35 vs 0.50±0.24for TNF-α and VEGF respectively, P＞0.05) and M14 (1.20±0.25vs 1.04±0.26 and 0.65±0.18 vs0.53±0.25 for TNF-α and VEGF respectively, P＞0.05). And the expression of TNF-α and VEGF in M21 was significantly higher than that in M7(2.23±0.30 vs 1.14±0.38 and 1.65±0.38 vs 0.67±0.35 for TNF-α and VEGF respectively, P＜0.01) and M14 (2.23±0.30vs 1.20±0.25 and 1.65±0.38 vs 0.65±0.18 for TNF-α and VEGF respectively, P＜0.01), but there was no difference between M7 and M14 (1.14±0.38 vs 1.20±0.25 and 0.67±0.35vs 0.65±0.18 for TNF-α and VEGF respectively, P ＞0.05).CONCLUSION: In the development of esophageal varices in portal hypertensive rats, increased TNF-α and VEGF may be not an early event, and probably play a role in weakening the esophageal wall and the rupture of esophageal varices.