A formulation to treat ocular conditions such as dry eye disease, as well as other conditions, is disclosed. Rapamycin and/or ascomycin is administered intraocularly, such as by topical application, injection into the eye, or implantation in or on the eye. For example, a topical administration may contain between about 50 pg/ml drug to about 50 μg/ml drug in a formulation which may be applied at bedtime or throughout the day. For injection, a dose of about 50 pg/mi to about 200 μg/ml may be used. Rapamycin and/or ascomycin may also be administered in milligram quantities as a surgical implant, for example, in a diffusible walled reservoir sutured to the wall of the sclera, or may be contained within an inert carrier such as microspheres or liposomes to provide a slow-release drug delivery system.