Objective:To study the protective effect of rosiglitazone, a specific peroxisome proliferator-activated receptor-γ(PPARγ) ligand on acute necrotic pancreatitis and pancreatitis-associated pulmonary injury. Methods:Fifty Sprague-Dawley(SD) rats were randomly divided into five groups, the control group, the sham operation group, the ANP group, the prophylactic treatment group and the therapeutic treatment group. In the acute necrotic pancreatitis group, rats were given two intraperitoneal injections of L-arginine while the control group did not receive anything, the sham operation group received the same volume injections of 0.9% saline solution. For the prophylactic treatment group, rats were given with rosiglitazone two times at an hour interval 30 min prior to the induction of pancreatitis. For the therapeutic treatment group, rats were given with rosiglitazone two times at an hour interval 30 min after the induction of pancreatitis. Amylase(AMY), TNF-α and IL-1β in blood plasma, lung myeloperoxidase(MPO) activity were evaluated. Pancreatic and pulmonary pathology were observed. Results:The levels of serum AMY,IL-1β,TNF-α and lung MPO in rats with acute necrotic pancreatitis were significantly higher than the those of control and sham operation group(P < 0.001); Compared with ANP group, the levels of serum AMY,IL-1β,TNF-α and lung MPO were significantly lower in the prophylactic and therapeutic group with rosiglitazone(P < 0.001) and pancreatic and pulmonary pathological injury were significantly reduced(P < 0.001). Conclusion:Both prophylactic and therapeutic treatments with rosiglitazone could ameliorate pancreatic and pulmonary injury induced by L-arginine, as observed by biochemical and histopathological study. The protective action of rosiglitazone may be linked to inhibition of TNF-α and IL-1β expression.