NK and NKT cells play important roles in both the pathogenesis and regulation of autoimmune disease. In this study, NK and NKT cells in the periphery and in the inflamed eyes of Lewis rats developing uveitis were quantified and evaluated for function. The number and phenotype of NK/NKT cells in the inflamed eyes and spleens were determined. The cytotoxic and suppressive activity of the eye-infiltrating NK/NKT cells was also studied. In rats with interphotoreceptor retinoid-binding protein (IRBP)-induced uveitis, the number of NK/NKT cells declined in the periphery, but increased in the eyes. The eye-infiltrating NK/NKT cells inhibited cytokine production by autoreactive T cells in vitro and had a weak cytolytic effect on NK-sensitive YAC-1 cells and NKT-sensitive U937 cells in vitro. Our study shows that the number of NK and NKT cells decreases in the periphery of rats with autoimmune uveitis. It is discussed whether the changing number of NK/NKT cells allows the escape from immune surveillance of uveitogenic (i.e. autoreactive) T cells and the development of intraocular inflammation, and the increased infiltration of the inflamed eye by suppressive NK/NKT cells favors rapid recovery from disease.