Objective: To compare the effect of laparoscopic D2 gastrectomy and open D2 gastrectomy on inflammatory reaction in patients with gastric cancer. Methods: The 96 patients with gastric cancer were randomly divided into laparoscopic group and open group. Patients in laparoscopic group were given treatment of laparoscopic D2 gastrectomy, and those in open group were accepted treatment of open D2 gastrectomy. The levels of CRP, IL-6, TNF-α and IL-10 were compared before operation and after operation. Results: The blood loss of laparoscopic group significantly lower than open group, operation time, postoperative exhaust time and postoperative ambulation time less than open group, the difference was statistically significant (P<0.05); the levels of CRP, IL-6, TNF-α and IL-10 at 1 day after operation were significantly higher than before operation, the difference was statistically significant (P<0.05); the levels of CRP, IL-6 and TNF-α of laparoscopic group after operation lower than open group, the levels of TNF-α higher than open group, the difference was statistically significant (P<0.05). Conclusion: Compared with open D2 gastrectomy, laparoscopic D2 gastrectomy has a significant advantage in small trauma, slight inflammatory reaction. It can be applied in clinical practice.