Purpose. To describe the presence of secretory leukocyte protease inhibitor (SLPI), a cationic peptide with antimicrobial and antiprotease activity in the innate immune reaction in a rat model of Staphylococcus aureus keratitis. Methods. Forty female Lewis rats were divided into 2 groups: the infectious keratitis and the epithelial defect groups. Eyes were processed for immunohistochemical studies for SLPI, interleukin-1, interleukin-6, tumor necrosis factor-alpha, and matrix metalloproteinase-8. Results. Immunohistochemical studies confirmed high levels of SLPI, IL-1, IL-6, TNF-α, and MMP-8 expression in eyes with S. aureus keratitis and with epithelial defects, in contrast to undetectable SLPI expression in the normal control corneas. Conclusions. To our knowledge, this paper is the first to demonstrate the presence of SLPI with increased amounts of proinflammatory cytokines in inflamed and infected corneas.