Objectives: The aim was to evaluate the effect of high molecular weight protein fraction of Calotropis procera latex on edema formation and oxidative stress in carrageenanâinduced paw inflammation. Methods: A subâplantar injection of carrageenan was given to induce edema in the hind paw of the rat. The inhibitory effect of high molecular weight protein fraction of C. procera latex was evaluated following intravenous administration (5 and 25 mg/kg body weight) and was compared with that of diclofenac given orally (5 mg/kg). The levels of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and myeloperoxidase (MPO) were measured in the inflamed paw tissue at the end of the study. Results: The high molecular weight protein fraction obtained from the latex of C. procera produced a doseâdependent inhibition of edema formation that was accompanied by normalization of levels of oxidative stress markers (GSH and TBARS ) and MPO, a marker for neutrophils in the paw tissue. Conclusions: The high molecular weight protein fraction of C. procera latex ameliorates acute inflammation in the paw through its antioxidant effect.