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AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on development of severe acute pancreatitis (SAP) and expression of nuclear factor-kappa B (NF-κB)and intercellular adhesion molecule-1 (ICAM-1) in the pancreas.METHODS: Male Sprague-Dawley (SD) rats (160-200 g)were randomly allocated into three groups (n = 18in each group): severe acute pancreatitis group,pioglitazone group, sham group. SAP was induced by retrograde infusion of 1 mL/kg body weight 5% sodium taurocholate (STC) into the biliopancreatic duct of male SD rats. Pioglitazone was injected intraperitoneally two hours piror to STC infusion. Blood and ascites were obtained for detecting amylase and ascitic capacity. Pancreatic wet/dry weight ratio, expression of NF-κB and ICAM-1 in pancreatic tissues were detected by immunohistochemical staining. Pancreatic tissue samples were stained with hematoxylin and eosin (HE)for routine optic microscopy.RESULTS: Sham group displayed normal pancreatic structure. SAP group showed diffuse hemorrhage,necrosis and severe edema in focal areas of pancreas.There was obvious adipo-saponification in abdominal cavity. Characteristics such as pancreatic hemorrhage,necrosis, severe edema and adipo-saponification were found in pioglitazone group, but the levels of those injuries were lower in pioglitazone group than those in SAP group. The wet/dry pancreatic weight ratio,ascetic capacity, serum and ascitic activities of anylase in the SAP group were significantly higher than those in the sham group and pioglitazone group respectively (6969.50 ± 1368.99 vs 2104.67 ± 377.16, 3.99 ± 1.22 vs 2.48 ± 0.74, P ＜ 0.01 or P ＜ 0.05). According to Kusske criteria, the pancreatic histologic score showed that interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma hommorrhage in SAP group significantly differed from those in the sham group and pioglitazone group (7.17 ± 1.83 vs 0.50 ±0.55, 7.67 ± 0.82 vs 6.83 ± 0.75, P ＜ 0.01, P ＜ 0.05.The expression of NF-κB and ICAM-1 in sham group was lower than that in SAP group and pioglitazone group (0.50 ± 0.55 vs 33 ± 1.21, P ＜ 0.01). There was a significant difference in the expression of NF-κB and ICAM-1 between SAP group and pioglitazone group (7.50±1.05 vs 11.33 ± 1.75, 0.80±0.53 vs 1.36 ± 0.54,P ＜ 0.01 or P ＜ 0.05) at 12 h after the induction of pancreatitis.CONCLUSION: Pioglitazone attenuates the severity of SAP. The beneficial effect of pioglitazone is multifactorial due to its anti-inflammatory activities, most likely through the inhibition of ICAM-1 expression and NF-κB activation. Specific ligands of PPARγ may represent the novel and effective means of clinical therapy for SAP.