OBJECTIVE： To study the protective effect of Glycyrrhiza uralensis polysaccharide （GUP） on CCl4 induced acute liver injury in mice and its mechanism. METHODS： 60 ICR mice were randomly divided into normal control group （normal saline）， model group （normal saline）， bifendate group （positive drug， 100 mg/kg） and GUP high-dose， medium-dose and low-dose groups （400， 200 and 100 mg/kg）. They were given relevant medicine intragastrically once a day. 15 d later， acute liver injury model was induced by intraperitoneal injection of CCl4 in those groups except for normal control group， and liver index was determined. The levels of AST and ALT in serum， the NOS， NO， SOD， GSH-Px and MDA levels in liver tissues were detected. RESULTS： Compared with normal control group， the liver index， the levels of AST and ALT in serum and NOS， NO and MDA in liver tissue increased in model group， while SOD and GSH-Px levels in liver tissue decreased （P＜0.05）； liver cells became swelling， degeneration and necrosis， showed obvious inflammatory injury. Compared with model group， the liver index of GUP groups decreased， there was statistical significance in GUP high-dose medium-dose groups （P＜0.05）； the levels of AST and ALT in serum and NOS， NO and MDA in liver tissue of mice decreased in GUP groups， while the level of SOD and GSH-Px in liver tissue increased （P＜0.05）； liver cellular swelling， degeneration and necrosis relieved， and pathological injury had been improved. CONCLUSIONS： GUP has a certain protective effect on CCl4-induced acute liver injury in mice and its protective effect may be related to antioxidation， decrease of NOS and NO levels， and reduction of the production of free radicals.