Background: Angiogenic and anti-angiogenic factors play an important role in tumor biology and tumor recurrence after surgical resection. Antiangiogenic factors such as vascular endothelial growth factor (VEGF)-receptor 1 (sVEGFR1) and sVEGFR2, two soluble form receptor proteins of VEGF, are critical for angiogenesis. VEGF can be sequestered by soluble forms of these receptors, which result in decreasing VEGF amount available to bind to its receptor on vascular endothelial cell surface. This study aimed to investigate the influences of video-assisted thoracoscopic surgery (VATS) lobectomy and open by thoracotomy for early stage non-small cell lung cancer (NSCLC) on postoperative circulating sVEGFR1 and sVEGFR2 levels. Methods: Forty-eight lung cancer patients underwent lobectomy through either VATS (n=26) or thoracotomy (n=22). Blood samples were collected from all patients preoperatively and postoperatively on days 1, 3 and 7. ELISA analysis was used to determine the plasma levels of sVEGFR1 and sVEGFR2. Data are reported as means and standard deviations, and were assessed with the Wilcoxon signed-Rank test (P < 0.05). Results: For all patients undergoing lobectomy, postoperative sVEGFR1 levels on days 1 and 3 were markedly increased, while postoperative sVEGFR2 levels on days 1 and 3 were significantly decreased. Moreover, VATS group had significantly higher plasma level of sVEGFR2 postoperative in comparison with open thoracotomy (OT) on day 1 (VATS 6,953±1,535 pg/mL; OT 5,874±1,328 pg/mL, P < 0.05). Conclusions: Major pulmonary resection for early stage NSCLC resulted in the increased sVEGFR1 and decreased sVEGFR2 productions. VATS is associated with enhanced anti-angiogenic response with higher circulating sVEGFR2 levels compared with that with OT. Such differences in anti-angiogenic response may have an important effect on cancer biology and recurrence after surgery. © Journal of Thoracic Disease.