The present study aimed to investigate the mechanisms by which mannose protects the lung injury induced in rats with acute pancreatitis (AP). An AP combined with Acute Lung Injury (ALI) model was established. A total of 90 healthy adult male Sprague-Dawley rats (300±50g weight) were randomly divided into three groups: sham operation group (SO group), severe acute pancreatitis lung injury group (SAP group), and mannose intervention group (MT group). Subsequently, each group was divided into two subgroups based on the time passed from intervention, namely 6 and 12 h. Each subgroup comprised 15 rats. The ratio of wet/dry weight of the lung tissue exhibited no significant change at different time points in the SO group. This parameter was significantly increased in the SAP group compared with the SO group at each time point of the treatment (P less than 0.05) and it was significantly lower in the MT group than that in the AP group (P less than 0.05) and it was significantly increased in the AP group at each time (P less than 0.05) compared with the SO group. The levels of TNF-α in the lung tissue in the SO group exhibited no significant change at different time points, but they were significantly decreased in the MT group at each time point (P less than 0.05) compared with the SAP group. The mannose receptor (MR) mRNA and protein levels in the lung tissues exhibited no significant change at different time points. The mRNA and protein levels of MR in the SAP group were significantly decreased at each time point (P less than 0.05) compared with the SO group. The mRNA and protein levels of MR, in the lung tissue of the MT group were significantly increased at each time point compared with the SAP group (P less than 0.05). Mannose could reduce the injury caused to the lung tissue of rats with severe acute pancreatitis by up-regulation of the expression of MR mRNA and protein.