Abstract: Objective To examine expression of stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in rat cornea tissue and their role in corneal allograft rejection. Methods With 15 Wistar rats as the normal control group, 22 Wistar rats received autologous corneal graft transplantation, and 44 Wistar rats received transplantation of corneal graft from SD rats with penetrating keratoplasty. From the rats with allograft transplantation, 22 were selected randomly for treatment with TobraDex eye drops for 30 days after the operation (twice a day), and the remaining 22 rats were treated with normal saline only. Clinical assessment of the corneal grafts was carried out using Larkin’s method; histopathological observation, immunohistochemistry, and real-time quantitative PCR of the corneal grafts were performed on days 5 and 9 after the transplantation. Results Graft rejection occurred in none of the rats in autograft group. In rats treated with TobraDex, the graft survival time was significantly longer than that in rats with saline treatment (24 ± 0.32 vs 10 ± 0.36 days, P<0.001), and histopathological examination revealed numerous inflammatory cells and neovascularization in the allografts in the latter group. SDF-1 and CXCR4 mRNA expression in the corneal tissue increased significantly in rats receiving allograft transplantation and saline treatment (P<0.001 on day 5 and P<0.01 on day 5), and their expression was obviously lowered in rats with TobraDex treatment. Immunohistochemical examination revealed that the expression of SDF-1 and CXCR4, found mainly in the corneal epithelium and stroma, was significantly increased in the allografts in rats with saline treatment. Conclusion SDF-1/CXCR4 may participate in corneal graft rejection in rats early after transplantation possibly through the mechanism that SDF-1 specifically induces CXCR4+ cell maturation and chemotaxis toward the allograft to promote corneal neovascularization.