The present study was designed to evaluate whether IL-6 is produced locally or systemically following acute inflammation. Full-thickness scale burns were made on rats. Serum IL-6 levels (SIL-6) showed a constant time-dependent change with a single peak 6 hours after the burn. SIL-6 elevation was correlated with the ratio of burn area to total body surface area. The liver, spleen, lymph node and skin harvested after the burn secreted significantly higher amounts of IL-6 after tissue culture when compared with those taken from sham rats. The venous serum drainage from the burn site induced significantly higher IL-6 production of splenocytes than the arterial and control venous sera. In conclusion, IL-6 production is rapidly and systemically triggered by a humoral factor following acute inflammation in vivo, resulting in constant kinetics for SIL-6.