This study was conducted to compare the serum level of Cortisol and Interleukin-6 (Stress Response) on eighteen clinically healthy mongrel male dogs of different ages (1-2 years old) with body weight ranged between 17-25 kg. Dogs were classified into two main groups open cholecystectomy and laparoscopic one. Anesthesia and postoperative management were identical in both groups. Serum level of cortisol was evaluated as a marker to assess surgical trauma and pain where it was measured before the operation (time 0) to obtain base line value and at 4 hours postoperatively. In addition, serum level of Interleukin-6 (IL-6) was evaluated also before the operation and at 4 and 24 hours after the surgery as a marker for the degree of systemic reaction to wide range of trauma. There was a significant (P < 0.05) lower concentration of serum cortisol in the laparoscopic group at four hours postoperatively than in the open surgery group. Serum levels of IL-6 during laparoscopic cholecystectomy were found to be significantly (P < 0.05) lower than that during open cholecystectomy at 4 and 24 hrs postoperatively.  The current study concluded that the laparoscopic cholecystectomy with small skin incisions with the avoidance of open laparotomy and excessive manipulation of tissues can minimize surgical stress and provide more favorable postoperative conditions for dogs. This indicated that laparoscopic cholecystectomy is more recommendable than traditional open cholecystectomy.