The drug dichloromethylene diphosphonate (CL2MDP) encapsulated in liposomes depletes macrophages but not other immunocompetent cells. The authors investigated whether subconjunctival injection of CL2MDP containing liposomes (CL2MDP-LIP) could prolong survival of corneal allografts in rats. Male Fisher rats received orthotopic corneal grafts of Dark Agouti origin. Rats were treated postoperatively with subconjunctival injections of 0.1 ml CL2MDP-LIP at the time of transplantation and on days 2, 4, 6, and 8 after transplantation. Control groups received either liposomes containing phosphate-buffered saline subconjunctivally at the same time points or no additional treatment. Corneal grafts were evaluated every other day and were scored for neovascularization, opacity, and edema. Immunohistologic evaluation was performed 12 and 19 days after surgery. Corneal grafts in both control groups were rejected within 17 days. In the Cl2MDP-LIP treated rats, grafts were not rejected during the maximum follow-up of 100 days. Cellular infiltration in these grafts was clearly reduced. There was also a strong reduction in neovascularization of the cornea. Rejection of orthotopic allogeneic corneal grafts could be prevented by repeated subconjunctival injection of Cl2MDP-LIP.