The effect of iron was studied in rats in a ROS‐initiated model of acute skin inflammation. Iron dextran was administered i.v. 24 h before the induction of the inflammatory response by intradermal injection of glucose oxidase attached to polyethylene glycol (GOD–PEG). Iron exacerbated the response at 24 and 48 h (P>0.001). Histologically, a similar picture was seen to that without iron except for an increase in tissue oedema and matrix destruction including the skin glands. Associated with iron loading was an increase in Perls stainable iron in the skin (P>0.025) and liver (P>0.001). However, skin inflammation without iron loading also increased skin iron levels (P>0.025). Total serum iron was decreased in iron‐loaded and GOD–PEG animals (P>0.01) and the unbound iron binding capacity (UIBC) increased (P>0.01).