Neuropsychiatric symptoms occur in systemic lupus erythematosus (SLE), a complex, autoimmune disease of unknown origin. Although several pathogenic mechanisms have been suggested to play a significant role in the etiology of the disease, the exact underlying mechanisms still remain elusive. Several inbred strains of mice are used as models to study SLE, which exhibit a diversity of central nervous system (CNS) manifestations similar to that observed in patients. This review will attempt to give a brief overview of the CNS alterations observed in these models, including biochemical, structural and behavioral changes.