The sclera is a dense fibrous and viscoelastic connective tissue. It forms the outer coat frame of the eye to keep the shape of eyeball by enduring the pressure from outside and inside. In eutherian mammals, the entire sclera consists of fibrous and type I collagen-dominated extracelluar matrix. Recent research has showed that the sclera is a dynamic tissue, capable of responding rapidly to changes in the visual environment to alter ocular size and refraction. Sclera’s biochemical and biomechanical properties determine the shape and size of the eyeball and therefore play an important role in determination of refraction status. Scleral extracellular matrix remodeling is responsible for changes in ocular elongation disease such as myopia. Diseases in sclera such as refractory scleritis and scleromalsia are all difficult to cure and often lead to blindness. It is speculated that sclera cells might play an important role in scleral remodeling or sclera inflammation. Although tissue-specific postnatal stem cells have been isolated from a variety of organs and tissues, it is still unknown whether sclera contains stem/progenitor cells. The purpose of this study is to identify multipotent scleral stem/progenitor cells (SSPCs) from murine sclera. We found that SSPCs possessed clonogenic and self-renewing capacities. They were positive for mesenchymal markers Sca1, CD90.2, CD44, CD105, CD73, and negative for hematopoietic markers CD45, CD11b, Flk1, CD34, CD117. In addition to express stem cell genes ABCG2, Six2, Notch1 and Pax6, SSPCs were able to differentiate to adipogenic, chondrogenic, and neurogenic lineages. This study indicated that sclera contained multipotent mesenchymal stem cells SSPCs. Further study of SSPCs may benefit understanding molecular mechanism of sclera diseases such as scleritis and myopia.