OBJECTIVE To study the effects of milk processing method on the content of esculentoside A and hepatotoxicity in Mongolian medicine Phytolacca acinosa. METHODS High performance liquid chromatography-evaporative light-scattering detection was used to determine the content of esculentoside A in raw P. acinosa， milk-soaked P. acinosa and milk-boiled P. acinosa. The rats were randomly divided into normal group， raw P. acinosa group， milk-soaked P. acinosa group and milk-boiled P. acinosa group， with 10 rats in each group. Except for the normal group， the rats in the remaining groups were administered corresponding medicinal solutions at a dose of 0.8 g/kg once daily for 15 consecutive days. After the last administration， the levels of biochemical markers [alanine transaminase （ALT）， aspartate transaminase （AST）] and inflammatory factors [interleukin-2 （IL- 2）， IL-6， tumor necrosis factor- α （TNF- α）] in plasma of rats， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in liver tissue， were determined. The pathological changes of liver tissue in rats were observed. RESULTS The contents of esculentoside A in raw P. acinosa， milk-soaked P. acinosa and milk-boiled P. acinosa were 6.46-6.59， 4.79-4.89， 5.04-5.14 mg/g， respectively. Compared with the normal group， the plasma levels of ALT， AST， IL-2 and TNF-α in rats were increased significantly in the raw P. acinosa group （P＜0.05）， while the level of SOD in liver tissue was decreased significantly （P＜0.05）； scattered punctate necrotic foci were observed within the hepatic lobules， and hepatocytes exhibited slight vacuolar degeneration. Compared with the raw P. acinosa group， the levels of ALT and AST in plasma of rats and the level of MDA in liver tissue were all decreased significantly in the milk-soaked P. acinosa group and the milk-boiled P. acinosa group （P＜0.05）， while the level of SOD in liver tissue was increased significantly （P＜0.05）. The plasma level of TNF-α in the rats of the milk-soaked P. acinosa group and the plasma levels of IL-2 and IL-6 in the rats of the milk-boiled P. acinosa group were all decreased significantly （P＜0.05）； additionally， the degree of liver injury was markedly alleviated in both groups. CONCLUSIONS The content of esculentoside A and hepatotoxicity both decrease after processing Mongolian medicine P. acinosa using the milk processing method.