OBJECTIVE： To study the protective effects of Mongolian medicine Lomatogonium rotatum water extract against acute liver injury in mice caused by D-GlaN and CCl4. METHODS： 60 mice were randomly divided into normal group （normal saline）， D-GlaN model group （normal saline）， positive control group （Kuihua hugan tablet， 0.56 g/kg） and L. rotatum water extract high-dose， medium-dose and low-dose groups [3， 1.5， 0.75 g（crude drug）/kg] 10 rats in each group. They were given relevant medicine intragastrically once a day for consecutive 23 days. 30 min after last administration， those group were given D-GlaN ip to induce acute liver injury model except normal group. The activity of AST， ALT， ALP， and acetylcholinesterase （CHE） content in serum were detected， and liver index was calculated. Liver histopathology was observed and scored. Other 60 mice were selected， and then grouped， given medicine and detected in lab index with same method with above group， except for modeling method （ig， 0.1％ CCl4）. RESULTS： Compared with normal group， necrosis or degeneration of liver cells were obvious in 2 model groups， pathological score， the activity of AST， ALT and ALP increased while CHE content decreased； liver index of D-GlaN model group increased while that of CCl4 model group decreased （P＜0.05）. Compared with D-GlaN model group， the activity of AST， ALT and ALP and liver index decreased in L. rotatum water extract groups， while CHE content increased （P＜0.05）； pathological morphology had been improved， and pathological score decreased. Compared with CCl4 model group， ALT activity decreased in L. rotatum water extract low-dose group， while CHE content and liver index increased； CHE content of L. rotatum water extract medium-dose group decreased， while liver index increased； the activity of AST， ALT and ALP decreased in L. rotatum water extract high-dose group， while CHE content increased （P＜0.05）. Pathological morphology of L. rotatum water extract groups had been improved to certain extent， and pathological score decreased. CONCLUSIONS： L. rotatum water extract could protect acute liver injury in mice induced by D-GlaN and CCl4.