Objective To investigate the effects of inflammatory reaction of thymomas with myasthenia gravis (MG) treated by traditional thoracotomy and minimally invasive surgery. Methods A total of 40 thymomas patients (Mssaoka Ⅰ or Ⅱ) with myasthenia gravis from August 2014 to June 2015 were treated by traditional thoracotomy (n=20) or video-assisted thoracoscopic surgery (n=20). The serum levels of IL-6, IL-8, TNF-α, CRP and CORT were measured by enzyme-linked immunosorbent assay (ELISA) methods at before anesthesia (T1), after anesthesia (T2), 2 h after skin cut (T3), 24 h post-operation (T4), 48 h post-operation (T5) and 72 h post-operation (T6) respectively. Perioperative parameters were also reported. The statistics analysis was performed by SPSS 17.0 software. Results The serum levels of IL-6, IL-8, TNF-α, CRP and CORT had no significant difference between T1 and T2, T2 and T3 (allP value>0.05) in both groups. But the serum levels of these factors after operation were obviously higher than that of before operation, commonly the highest level was reached at T4 (allP value>0.01), and also was higher at T6 than that of before the operation (allP value<0.01), except the level of TNF-α recovered rapidly to the level of before operation (allP value>0.05) in the VATS group. The operation time, postoperative drainage tube indwelling time and incision healing time in the VATS were lower than that in the control group (allP value<0.05). Conclusion VATS could be widely applied in clinical practice with lowering operative trauma and reducing the degree of inflammatory reaction.