The study was designed to investigate the relationship between enteric neurons (EN) damage and natriuretic peptides (NPs) signaling pathway in STZ-induced diabetic mice.hnmunohistochemistry and western blot were used to investigate the expression level of nNOS and NPs receptors (NPRs) in gastric fundus (GF).The results showed that the number of enteric NOS neurons was decreased, and the expression levels of eNOS and nNOS were significantly down-regulated, however, the expression levels of NPR-A, B and C were all increased in diabetics.CNP can decrease eNOS and nNOS expression in cultured gastric myocytes and GF.Electrical field stimulation (EFS)-induced relaxation was significantly suppressed while the contraction was enhanced in diabetic GF.The results suggest that up-regulation of NPs signalling pathway maybe involved in loss of enteric NOS neurons in diabetic GF.