Background Surgical trauma may be associated with enhanced tumor growth and establishment. The authors studied the effect of carbon dioxide (CO2) pneumoperitoneum versus laparotomy on tumor necrosis factor-a (TNFa), migration inhibitory factor (MIF) expression, and nuclear factor kappa B (NFjB) activity in human gastric cancer. Methods Nude mice were inoculated intraperitoneally with human gastric cancer cells (MKN45). Then laparotomy, CO2 pneumoperitoneum, and anesthesia alone were performed randomly. Tumor growth and associated TNFa and MIF expression and NFjB activity were determined. Results Total tumor weight, especially at the anterior abdominal wall, was higher after laparotomy than after CO2 pneumoperitoneum (p�.05). The mRNA expression of TNFa was higher 24 and 48 h after laparotomy than after CO2 pneumoperitoneum (p�.05 and p�.01, respectively). At all the examined time points, MIF mRNA expression also was higher after laparotomy than after CO2 pneumoperitoneum (p�.05 until 1 week or p�.01 at 2 weeks). The NFkB protein was more activated after laparotomy than after CO2 pneumoperitoneum 6 h subsequent to surgical procedures. Conclusion After CO2 pneumoperitoneum, tumors have less TNFa and MIF expression and less NFjB activity than after laparotomy. This may be associated with less tumor growth, supporting minimal invasive techniques in gastrointestinal oncologic surgery.