Severe acute pancreatitis (SAP) is a serious necro-inflammatory disease with a high mortality rate due to lack of specific treatments. Previous studies have shown that panaxadiolsaponins (PDS) involved in the regulation of immune function and protection against cell injury. The aim of our study was to investigate the protective effects of PDS on liver and kidney injury in rats with SAP. Sixty-four rats were divided into four groups (n=16): Sham Operation (SO) group, SAP group, Dexamethasone (DEX) group and PDS group. The results showed that PDS significantly decreased the level of serum AMS and GLU of SAP rats (P<0.05), while DEX did not affect the level of serum AMS and GLU. DEX retarded the increasing of serum Hb and HCT of SAP rats (P<0.05), and PDS retarded the increasing of Hb, RBC and HCT (P<0.05). DEX and PDS significantly decreased the level of serum BUN, TNF-alpha and IL-6 (P<0.01). Results of pathological analysis showed that PDS could protect against liver and kidney injury in SAP rats. To the best of our knowledge, this is the first report that PDS could protect against liver and kidney injury in SAP rats and had better therapeutic effects than DEX, indicating a potential drug to be used in treating SAP.