The ocular surface is a delicate structure that susceptible to injury and infection. Ulcerative keratitis is a painful eye condition characterized by stromal infection, ulcerative epithelium, decreased vision and cornea scar. Due to the reason that formation of vascularization, fibrosis or scarring in corneal epithelium can cause disastrous effects on vision, inflammatory response in the eye must be tightly controlled in space and time. Ocular innate defense system consists of antimicrobial peptides and immune cells that secreted or accumulated at the surface; they work in concert to eliminate intruding pathogens. Under normal circumstances, innate immunity suffices in providing quick, non-specific protection against infection. As opposed to adaptive immunity which usually takes longer and thus has more destructive effects on ocular tissues, innate immunity is more benign as its occurrence is restricted to superficial tissues such as eyelid, limbus and conjunctiva, of which the blood supplies bring immune cells to the inflamed sites for clearance of microbial and apoptotic cell debris. Surface-tension associated proteins (SP) that present in corneal epithelium and tear fluid has emerged as the new player in innate immunity of the eye. In this study, function of SP protein in corneal innate immune modulation was evaluated by using a human corneal epithelial cell line. Cells were depleted of SP by transfecting with short interfering RNA and stimulated cytokine production was determined. Conversely, exogeneous SP was found to reverse the impaired immune response in SP-depleted cells in a dose-dependent manner. This study is the first to demonstrate the role SP as immune-regulator in corneal epithelium. Combined with their known activity in direct killing of bacteria, SP may have therapeutic implications in ocular infectious diseases.