Experimental models for antipospholipid syndrome (APS) have been established recently in lupus-prone mice and induced in naive mice. The induction of APS is performed by passive infusion or active immunization of antiphospholipid antibodies (aPL) or the cofactor beta 2GP-1. High levels of diverse aPL develop in the animals in conjunction with clinical manifestations similar to the human disease, entailing low fecundity rate, fetal resorptions, thrombocytopenia, prolonged activated partial thromboplastin time, and neurological and behavioral impairments. The pathogenicity of aPL was confirmed in an in vivo thrombosis model. Immunomodulation of APS manifestations and treatment regimens in the experimental models are discussed.