Multiple sclerosis is a chronic progressive demyelinating disease of the central nervous system. At present, systemic drug therapy for multiple sclerosis has limited efficacy and serious side effects. Everolimus, as a new generation of mTOR inhibitors, can effectively alleviate the inflammatory reaction of the central nervous system and offers a promising choice for the treatment of multiple sclerosis. However, due to the low oral bioavailability and narrow response window of oral everolimus, a new delivery system is urgently needed to overcome the above problems. In this study, we constructed a tip-concentrated microneedle patch as a transdermal delivery system of everolimus for the treatment of multiple sclerosis. Here, the drug was concentrated in the needle tips by the rational design, making it delivered completely into the skin. The therapeutic effect of everolimus-loaded microneedles was evaluated using the experimental autoimmune encephalomyelitis (EAE) model and further verified with neurological function scores and the histopathological results of the spinal cord. These results indicated that the tip-concentrated microneedle patch provided an effective, safe and simple method for the transdermal delivery of everolimus, thus providing a new treatment for multiple sclerosis.