Purpose: We assessed the combined use of Staphylococcal Enterotoxin B (SEB) superantigen pre-treatment along with allogeneic bone marrow transplant (BMT) to induce immune suppression condition and inhibit corneal keratoplasty rejection in mice. Methods: BALB/C (H-2d) mice were both BMT and corneal allografts donors and C57BL/6(H-2b) mice were recipients. Prior to BMT, recipients received single injections of either SEB, cyclophosphamide (CYP), or normal saline (NS). Allogenic corneal penetrating keratoplasty was performed 7 days after BMT. Bone marrow chimerisms in recipients (donor major histocompatibility complex-II H2-d) were determined on Days 14, 28, and 56 post-BMT. Recipient immune response was assessed by mixed lymphocyte reactions (MLR) using splenocytes from C57BL/6 mice as responders in co-culture with stimulator cells from C57BL/6 (isogeneic), BALB/C (allogeneic), or CBA/1(third party) mice. Cluster of differentiation 4 receptors positive (CD4+) and CD8+T cells in recipient mice were evaluated. Corneal graft survival was assessed using Kaplan-Meier survival curves. Results: SEB pre-treatment induced higher levels of hematopoietic chimerism on Days 14, 28 and 56 post-BMT than did CYP or NS pre-treatment. Mean corneal allograft survival was significantly prolonged with group SEB-BMT (20.3 +/- 7.6 days) compared to group CYP-BMT (13.0 +/- 4.0 days) and NS-BMT (9.0 +/- 2.2 days). SEB-BMT mice splenocytes had diminished MLR responses compared to CYP-BMT or NS-BMT mice. CD4+ and CD8+T cells in peripheral blood and spleens were significantly reduced in group SEB-BMT mice. Conclusions: BMT after SEB pre-treatment could promote mixed chimerism, which inhibited allogeneic cornea transplant rejection. This should possibly relate to CD4+ and CD8+T cell deletion and acquiring donor-specific immunosuppression.