Systemic lupus erythematosus encephalopathy (NPSLE) is a nervous system complication of systemic lupus erythematosus (SLE). Various animal models of NPSLE have been developed that are characterized by histological defects, such as neuronal apoptosis and fewer synapses; brain leukocyte infiltration; and behavioral defects, such as emotional abnormalities and impaired learning and memory. In this article, we summarize the method used to construct animal models of NPSLE, describe the principal characteristics of each, and discuss the use of these models in the study of the pathogenesis of the disease and the identification of potential therapeutic targets. These models are useful means of defining the pathogenesis of NPSLE, screening potential therapies, and developing techniques for personalized diagnostic and treatment plans.