AbstractNeural tube defects (NTDs) were demonstrated to occur at a high rate (29.4%) in non‐obese diabetic (NOD) mouse embryos on day 13 of gestation. Macro‐scopically, three different forms of NTDs were observed: the combined form of exen‐cephaly and myeloschisis, the pure form of exencephaly, and that of myeloschisis. The neural walls of the open tube were everted bilaterally. It was microscopically demonstrated that NTDs were composed of not only the everted neural walls but also voluminous mesenchymal tissue adjacent to the everted neural walls. The everted neural wall had three‐layered structure made up of outer, intermediate, and inner zones. The morphological findings of the intermediate and inner zones were similar to those of mantle and marginal layers in the normally closed neural tube. However, the outer zone, which corresponded to the ependymal layer in the normal neural tube, had characteristic findings. Namely, the cells were small, round and uniform in shape. Almost no mitotic figures were observed in this zone, and electron microscopic investigation revealed few cytoplasmic organelles. Of 9 NOD mouse embryos with NTDs, 2 exhibited duplicated notochords. In one of these two embryos, an aberrant tubal structure was formed of neural tissue. The plausible causes of NTDs in NOD mouse embryos were discussed based on these f