Our major findings are as follows: (1) VCAM-1 protein levels were increased in retinal vessels of wt mice after 8 weeks of diabetes, at a time-point when the expression of the inflammatory cytokines TNFα, IL-6 and IL-1β was elevated in retina and levels of sVCAM-1 in plasma were higher; (2) TNFα−/− deficient mice exhibited higher basal levels of VCAM-1 protein in retinal vessels and sVCAM-1 in plasma than wt mice, but failed to up-regulate IL-6 and IL-1β mRNA and VCAM-1 protein in response to diabetes. The gene discussed is TNF; the disease is diabetes mellitus.