Injury to the human body alters normal physiology across several systems and these alterations are proportional to the extent of the injury. Physiological response to minimally invasive surgery appears to be different than those of traditional open surgery. Acute phase protein response appears to be one example. The important cytokines that are known as major mediators of acute phase response are interleukin-6 and TNF-alpha. Thirty patients were studied in which 14 underwent open cholecystectomy and 16 laparoscopic cholecystectomy. Three blood samples were taken from each patient, one pre-operatively and 2 post operatively at 4 and 24 hours. Interleukin-6 and Tumour Necrosis Factor-alpha (TNF-alpha) were raised significantly in post operative blood sample in both groups but the rise was much more in open group than laparoscopic group. This suggest less stress response in laparoscopic group which also showed a direct effect on patient convalescence in terms of less pain, less analgesic requirement and shorter hospital stay