Diabetic retinopathy (DR) is the common cause of diabetic vascular complications. The NOD-like receptor (NLR) family, pyrin domain containing 1 (NLRP1), also known as NALP1, inflammasome is the first member of the NLR family to be discovered, playing an important role in inflammatory response. However, its effect on DR development has not been reported. In the study, the wild type (WT) and NLRP1(-/-) mice were injected with streptozotocin (STZ) to induce DR. The results indicated that NLRPI significantly increased bodyweight reduction and decreased blood glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRPI in retinas. NLRPI ameliorated retinal abnormalities in DR mice using H&E staining. In addition, attenuated avascular areas and neovascular tufts were also observed in NLRP1(-/-)/DR mice. The levels of pro-inflammatory cytokines in serum and retinas were highly induced in WT/DR mice, whereas being markedly reduced by NLRPI In addition, vascular endothelial growth factor (VEGF) and Ibal expressions induced by STZ in serum or retinas were significantly down-regulated in NLRP1(-/-)/DR mice. Consistently, NLRP1(-/-) attenuated ASC and Caspase-1 expressions in retinas of DR mice. Compared to WT/DR group, NLRP1 markedly decreased retina p-nuclear factor-kappa B (NF-kappa B), interleukin-1 beta (IL-1 beta) and IL-18 levels. And similar results were confirmed in vitro that suppressing NLRPI/ASC inflammasome ameliorated inflammatory response in fructose-treated retinal ganglion cells. The results above indicated that the modulation of NLRPI inflammasome might be a promising strategy for DR therapy. (C) 2018 Published by Elsevier Inc.