Choroidal neovascularization (CNV) is a pathological feature which commonly occurs in ocular diseases. This condition is characterised by vasculogenesis and angiogenesis underlying the neuroretina, with retinal pigment epithelium (RPE) and choroid as main targets. Inflammation and immunity are crucial in the early development of CNV. Tumour necrosis factor (TNF) α-induced protein-8 like-2 (TIPE2 or TNFAIP8L2), a recently identified gene, is a negative regulator of innate and adaptive immunity which participates in inflammatory homeostasis. We determined the expression of TIPE2 in normal and inflamed RPE cells, and evaluated the relationship of TIPE2 with factors associated with inflammation and angiogenesis. TIPE2 is present in both the cytoplasm and nucleus of human RPE cells and is down-regulated in the inflammatory state with decreased cell viability. Knock-down of TIPE2 by a specific short interfering RNA increases the expression levels of TNF-α, IL-1β and angiogenic vascular endothelial growth factor (VEGF), particularly under the stimulation of lipopolysaccharide. In consideration of the vital role of VEGF in the final stage of neovascularization, the anti-inflammatory TIPE2 is also anti-angiogenic and may participate in CNV formation.