The course of acute pancreatitis (AP) is mild in most patients, but severe AP (SAP) is associated with high mortality. Early diagnosis of SAP is important for successful treatment, but remains difficult. One reason is the lack of early biomarkers with sufficient diagnostic accuracy for SAP. The aim of the study was evaluation of proteins associated with endothelial dysfunction in acute states, namely angiopoietin-2 and soluble fms-like tyrosine kinase-1 (sFlt-1), as early predictors of SAP. Serum concentrations of studied markers were measured among 70 patients with AP during first 24 and 48 hours from the onset of symptoms. High concentrations of both proteins were significantly associated with development of SAP, organ failure, including renal failure, and coagulopathy in the course of AP. Measurements of angiopoietin-2 and sFlt-1 in first days of AP may help in early prediction of severe course of the disease.