The enhanced production of cytokines is a hallmark of acute inflammation including inflammation occurring in the setting of surgical incision. Recent studies demonstrate that several cytokines participate in the enhancement of nociception which occurs after incision. Since opioids like morphine interact with neutrophils, macrophages and other immunocytes, it is possible that morphine exerts some of its antinociceptive action by altering the vigor of the local inflammatory response. In these studies we used a murine hind paw incisional model to study the role of morphine in modulating incisional inflammation. We measured the effects of pre-incisional morphine administration on nociceptive thresholds and cytokine production in incised skin. We also followed neutrophil infiltration in these wounds. In other experiments mice were treated with daily morphine injections for 4 days followed by hind paw incision and cytokine analysis in order to study the effects of chronic morphine administration. As expected, the incised mouse hind paws displayed profound allodynia within 30 minutes of incision and this effect was stable for several hours. Morphine dose-dependently reduced or reversed this sensitization. Skin samples harvested from these mice showed enhanced levels of 5 cytokines: IL-1beta, IL-6, tumor necrosis factor alpha (TNFalpha), granulocyte colony stimulating factor (G-CSF) and keratinocyte-derived cytokine (KC). Morphine dose-dependently reduced these incision-stimulated cytokine levels as well. Separate analyses measuring myeloperoxidase (MPO) and using immunohistochemistry demonstrated that morphine strongly and dose-dependently reduced the infiltration of neutrophils into the peri-incisional tissue. Chronic morphine pretreatment caused mechanical allodynia, but had no overall effect on incision-stimulated skin cytokine levels. The administration of morphine prior to incision reduces the expression of multiple locally produced cytokines possibly by reducing acute phase neutrophil infiltration. Chronic morphine treatment sensitizes skin, but does not have major effects on incision-stimulated cytokine production. These findings have implications surrounding pain management, risk of infection and wound healing.