Objective: To study the role of CD4+ natural killer T ( NKT) cells in staphylococcal- enterotoxin- B ( SEB)- treated rats after high- risk corneal transplantation. Method: Fisher 344 donor corneas were transplanted into Lewis recipients. Corneal neovascularization was induced by sutures. All the recipients were randomly divided into 3 groups. The SEB group was intraperitoneally injected with SEB at a concentration of 75 mu g/ kg. The drug combination group received SEB and dexamethasone at a concentration of 5 mg/ml. The control group received saline buffer. All transplants were evaluated for 30 days. Ten days after transplantation, 3 recipients in each group were sacrificed for immunological study. Result: The survival time of the allografts in the SEB group was 12.50 +/- 1.41 days, much longer than in the control group ( 7.30 +/- 0.67 days) and the drug combination group ( 10.38 +/- 3.07 days). The lymphocyte proliferation ability was the weakest and the percentage of CD4+ NKT cells in both the spleen and the mandibular lymph nodes was the highest in the SEB group, while the percentage of CD4+ and CD8+ cells was the lowest in the drug combination group. IL- 2 in the aqueous humor and the serum was lower while IL- 10 was higher in the SEB group than in the other 2 groups. Conclusion: SEB prolongs allograft survival in rat high- risk corneal transplantation. This effect seems to be mediated by the upregulation of CD4+ NKT cells. Copyright (c) 2007 S. Karger AG, Basel.