Background: Inflammatory response following surgical trauma has long been a matter of study. Results, however, have been varied. We sought to assess changes in the levels of proinflammatory and anti-inflammatory cytokines in patients undergoing laparoscopic and open cholecystectomy and their impact on the clinical outcome of patients concerning the postoperative pain score.Methods: The study involved 90 cholecystectomies (55 laparoscopic and 35 open) for chronic cholecystitis. Blood samples were collected 2 hours preoperatively and at 4 and 24 hours post surgery. Sera were evaluated for the levels of interleukin-1β, interleukin-10, and tumor necrosis factor-alpha. The independent sample t-test was used to compare the means of a variable between the 2 groups. Statistical analysis was done using SPSS, version 17.Results: The rise in the levels of interleukin-1β, interleukin-10, and tumor necrosis factor-alpha was significantly more in the open cholecystectomy group at 4 hours (P<0.00). At the 24th postoperative hour, the levels of all 3 cytokines were also higher in the open cholecystectomy group (P<0.001 for interleukin-1β, P=0.185 for interleukin-10, and P<0.001 for tumor necrosis factor-alpha). At the 4th postoperative hour, the patients in the laparoscopic cholecystectomy group had a significantly lower pain score (P<0.001) than the open group. Conclusion: Both laparoscopic and open cholecystectomy procedures altered the inflammatory milieu of our patients in the postoperative period. Inflammation caused by the laparoscopic procedure was significantly less. More research is needed to target specific inflammatory and anti-inflammatory cytokines to reduce surgical stress and improve patient outcomes.