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Background/Aim: In a previous study, we have demonstrated that hypertonic saline solution infusion significantly reduced mortality in experimental acute pancreatitis (AP) through an improvement in the hemodynamic conditions and by an anti-inflammatory response, but its effects on the pancreatic lesions were not evaluated. The present study was designed to evaluate whether the mortality reduction associated with hypertonic saline solution administration in acute pancreatitis is due to a local effect attenuating the pancreatic lesions or is a consequence of systemic inflammation response reduction. Methods: AP was induced in male Wistar rats by intraductal 2.5% taurocholate injection. Animals were divided in groups: C (without AP), NT (not treated AP), NS (AP treated with NaCl 0.9%), and HTS (AP treated with NaCl 7.5%). Ascitic fluid volume, trypsinogen activation peptide (TAP) and amylase levels in ascitic fluid and serum were determined. Pancreatic cyclooxigenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression were assessed by Western blot analysis. Pancreatic MPO, MDA, and histological studies were analyzed. Inflammatory cytokines (TNF-α, IL-6, and IL-10) levels in ascitic fluid, serum, and in pancreatic tissue were determined by ELISA. Results: There were no significant differences in serum and ascitic fluid TAP and amylase levels, and in pancreatic MPO, MDA and histological score in groups NT, NS and HTS. A significant decrease in pancreatic COX-2 and iNOS expressions were significantly decreased in the HTS group, as well as ascitic fluid volume and inflammatory cytokines levels in ascitic fluid, serum, and pancreatic tissue when compared to NT and NS groups. Conclusions: These findings suggest that hypertonic saline solution decreases local and systemic inflammatory response in acute pancreatitis without changing the intensity of the pancreatic lesions. Supported by FAPESP 2007/03980-5