Intracellular calcium overload plays a key role in severe acute pancreatitis. Resveratrol can decrease the severity of pancreatitis; however, the mechanism of action of resveratrol has not been determined. The aim of our study was to examine the relationship between calcium overload and the effects of resveratrol in severe acute pancreatitis. Animals were randomly divided into 3 groups: control group (sham operation), model group (0.1 ml/100 g of 3.5% sodium taurocholate used to induce severe acute pancreatitis), and treated group (treated with resveratrol, 10 mg/kg). In model group, the severity of pancreatitis was aggravated; this was evaluated by pancreatic weight/body weight and lung weight/body weight ratios, serum amylase activities, and pancreatic histopathological scoring; the Ca(2+)-Mg(2+)-ATPase and Ca(2+)-ATPase activities decreased while PLA(2) activity and [Ca(2+)](i) increased gradually with time. Compared to the control group, in the model group, these changes were observed in the pancreatic tissue at the 3 h time point and in the lung tissue at the 6 h time point. Resveratrol ameliorated the changes in the laboratory parameters and significantly reduced the pathological damage in the tissues at the corresponding time points. In conclusion, intracellular calcium overload leads to tissue damage in severe acute pancreatitis, and the beneficial effects of resveratrol appear to be mediated by reducing the intracellular calcium overload; this not only limits pancreatic cellular injury but also secondary lung injury.