OBJECTIVE To study the immunosuppressive effect and mechanism of cyclospoirne A (CsA) in a drug delivery system (DDS) implanted in the anterior chamber of corneal allograft in a mouse model. METHODS Female BALB-c mice were the recipients of corneal allografts from C57BL-6 donor mice. A total of 90 allografts were implanted in penetrating keratoplasty. Cyclosporine A was incorporated into a polyactide-coglycolide-co-caprolactone (PGLC) polymer and small pellets of CsA PGLC were placed into the anterior chamber of recipient mouse eyes at the time of transplantation. Control recipients did not receive any implants or received implants containing no drug. The clinical condition of the grafts was observed by slit-lamp microscope every three days and the tempo and the time of rejection of the grafts were recorded. Some grafts were removed at weekly intervals for histopathological and immunohistopathological analysis. RESULTS The corneal allografts of the mice with CsA PGLC implanted (group A) prolonged their survival time significantly with a median of 35 +/- 3 days. In contrast, the median survival time of corneal allografts in eyes of recipients receiving implants containing no drug (group B) and eyes receiving allografts but no implant (group C) was 14 +/- 3 days. The differences between A and B and between A and C group were statistically very significant (P < 0.001). The corneal donor of the eyes treated with the CsA PGLC implant remained clear until the implant pallet began to shrink in size and graft rejection began. The grafts which came under an immune attack progressively were vascularized and thickened, and became opaque. In the control animals, the development of the immune response overlapped with the acute inflammatory reaction, which occurred in the mouse eye following corneal transplantation. Histopathologically and immunohistopathologically, the grafts, ciliary body and iris which were subjected to an immune response contained a dense infiltrate of neutrophils, CD(4)(+) and CD(8)(+) T lymphocytes, and many CD(11B)(+) inflammatory cells including macrophages and Langerhans cells in the control rejection mice. This cellular infiltrate was decreased in the recipients, and delayed in ciliary body and iris whose corneas were transplanted with the CsA PGLC implant in the anterior chamber. CONCLUSIONS Intraocular CsA in a sustained release system as a means significantly prolongs corneal allograft survival in mouse model and protests corneal allografts from acute, immune-mediated rejection.