Aims: To study the role of sinomenine (SIN) in prolonging high-risk corneal graft survival in rats. Methods: All recipients were randomly assigned to SIN, cyclosporine A (CsA), SIN plus CsA and control groups. IL-2, IL-10, Fas-Fas ligand and CD4(+)CD25(+)FoxP3(+) T cells in peripheral blood were detected. In addition, rat corneal grafts' survival times were recorded. Results: Survival time was 15.88 +/- 5.87 days in the SIN group, 17.67 +/- 5.43 days in the CsA group and 20.75 +/- 4.77 days in the drug combination group, which were longer survival times than those in the control group (p < 0.05). Compared with the SIN and CsA groups, levels of CD4(+)CD25(+)FoxP3(+) lymphocytes in the control group were decreased (p < 0.05) and were increased in the cotreated group (p < 0.05). IL-2 levels in the SIN-only and CsA-only groups were lower than those in the control group (p < 0.05) and higher than those in the cotreated group (p < 0.05); however, the results for IL-10 were different. The expressions of Fas and Fas ligand were least in the control group. Conclusion: SIN could prolong allograft survival and might have potential clinical usage.