Background: Opium addiction alters immune responses to stresses such as an injury due to changing the secretion of cytokines. The present study assessed the effect of opium addiction on the cytokines [tumor necrosis factor α (TNFα), interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-10] before and after laparotomy. Methods: Male rats were randomly divided into control and opium addicted (n = 20). Then, cytokines were measured before surgery, immediately after surgery (within 30-60 minutes) and 24 hours after surgery. Findings: IFN-γ was raised in an addicted group in three phases of the study as compared to that of the control group. IL-4 in opium addicted group decreased in two phases after surgery compared to the control group. IL-4 was lower after surgery in comparison to before surgery in the opium addicted group. The difference in IL-10 and TNFα levels was not statistically significant in the all groups measured in three phases of the investigation. Conclusion: The results revealed that opium addiction can increase plasma level of IFN-γ in rats and decrease plasma level of IL-4 after surgical stress. It seems that opium addicted rats are a more susceptible to increased inflammation.