Over the past decade, accumulating evidence has indicated a crucial role for chemokines and chemokine receptors in the pathogenesis of autoimmune diseases in both human and mouse models. Locally secreted chemokines and their receptors are important mediators of leukocyte recruitment to the tissues, and contribute to the initiation and progression of autoimmune diseases. Thus, blockade of chemokine and chemokine receptor interactions has emerged as a novel therapeutic strategy. MRL/MpJ-lpr/lpr (MRL/lpr) and (NZB X NZW) F1 mice, the two strains of mice that develop spontaneous autoimmune disease closely resembling human systemic lupus erythematosus (SLE), are considered to be excellent models for investigating the pathogenesis of the human disease. In addition, similar expression patterns of chemokines and chemokine receptors in inflamed organs are shown in humans and lupus model mice, especially MRL/lpr mice. Therefore, findings obtained from experiments with lupus model mice may be applicable to the treatment of these autoimmune diseases in humans. In this article, we review the role of chemokines and chemokine receptors involved in the pathogenesis of autoimmune diseases and the therapeutic approach of chemokine blockade in lupus model mice.