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AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved.METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats.The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathological score of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs.RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase contentof the treatment group was significantly lower compared to the model group at 12 h (P ＜ 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P ＜ 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P ＜ 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively).Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P ＜ 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P ＜ 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P ＜ 0.05, 2.00 vs 0.00) and the sham operation group (P ＜ 0.01, 2.00 vs 0.00) at 12 h.No NF-κB expression in the lung was found in any group.CONCLUSION: Dexamethasone can lower the amylase,endotoxin and TNF-α levels as well as mortality of SAP rats. NF-κB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-κB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.