Abstract: Objective To observe the protective effect of atorvastatin on joint injury in ApoE- / - mice. Methods Forty ApoE- / - mice were randomly divided into a model group and a drug group. All mice were fed a high-fat diet. The drug group received atorvastatin 10 mg / (kg·d), and the model group received the same amount of normal saline. Twenty normal C57BL/ 6J mice (control group) were fed a normal diet. We used an automatic biochemical analyzer to detect changes in blood lipids, and ELISA was used to detect serum IL-6 and TNF-α concentrations. Knee joint tissue samples were harvested for HE staining and safranin O-fast green staining to observe tissue morphological changes, and transmission electron microscopy was used to observe chondral ultrastructural changes. Results Compared with the model group, serum TC, TG, and LDL-C concentrations in the atorvastatin ( drug) group were significantly decreased (P<0. 01), while HDL-C concentrations increased (P<0. 01), and the serum inflammatory factors, IL-6 And TNF-α decreased significantly (P< 0. 01). Chondral ultrastructural damage improved significantly with atorvastatin. Inflammatory cell infiltration in the synovial membrane of the knee joint decreased, as did the degree of cartilage tissue structural damage and ossification, which significantly delayed the disease process. Conclusions Atorvastatin can protect against joint damage in ApoE- / - mice by regulating blood lipids and down-regulating inflammatory factors.