Acute pancreatitis is a generally mild and self-limiting disease. However, about 10%-15% of patients with the condition can be severe, in whom a systemic inflammatory response and multiple organ failure occur. Despite huge improvements in intensive care treatment, no effective medical therapies are currently available to prevent this condition. Mesenchymal stem cells (MSCs) are capable of self-renewal, proliferation and differentiating into various cells, and they are being tested for their immunoregulatory activities and regenerative potential. Recently, MSCs have been reported as a stem cell-based therapy in experimental severe acute pancreatitis, which significantly reduced the inflammatory level, pancreatic edema and acinar cell degeneration. The combination of MSCs with Chinese herbal medicine has shown more potential for the treatment of severe acute pancreatitis. Thus, MSCs will be a promising tool for treatment of severe acute pancreatitis. However, in spite of these encouraging findings, the optimal dosage and detailed mechanisms need to be explored further.