Herpetic stromal keratitis (HSK) is a T cell-orchestrated, immunoinflammatory lesion that results from corneal Herpes simplex virus infection. Previous reports indicate an essential role for proinflammatory cytokine interleukin (IL)-1 in HSK pathogenesis. The present study evaluates the efficacy of IL-1 receptor antagonist (IL-1 ra) protein in the management of HSK. Mice receiving IL-1 ra had diminished disease severity. The administration of IL-1 ra was shown to reduce the influx into the cornea of cells of the innate and adaptive immune response. In addition, the treatment diminished corneal vascular endothelial growth factor levels, resulting in reduced angiogenic response. Our results show the importance of targeting early proinflammatory molecules such as IL-1 to counteract HSK and advocate IL-1 ra as an effective agent to achieve this.