BackgroundDiabetes can result in pathological changes to enteric nervous system. Our aim was to test the dynamic changes of enteric neurons and identify the role of enteric glial cells (EGCs) in regulating enteric neuron expression in diabetic rats. MethodsA single injection of streptozotocin (STZ) was used to establish diabetic rats. Animals were randomly distributed into diabetic 1-, 4-, 8-, and 16-week groups, as well as age-matched control groups. The PGP9.5- and glial fibrillary acidic protein (GFAP)-immunopositive cells were quantified by immunohistochemistry. The protein levels of PGP9.5, ChAT, nNOS, S-100, and c-fos were determined by western blotting. The levels of nerve growth factor (NGF), neurotrophin 3 (NT-3), and glial cell-derived neurotrophic factor (GDNF) were tested by ELISA. Key ResultsAn increase in blood glucose and a decrease in body weight were observed following STZ administration. PGP9.5 expression did not change in the diabetic ileum. However, ChAT increased after 16weeks, and nNOS decreased after 8 and 16weeks in theilea of diabetic rats. The absence of degeneration of enteric neurons during the acute stage of the disease could be the consequence of the up-regulation of GFAP, S-100, and c-fos. Moreover, the content of NGF, NT-3, and GDNF in theileum increased by varyingdegrees after 1 and/or 4weeks of diabetes. Using 2 co-culture models of EGCs and SH-SY5Y cells ina highglucosecondition, the supportive role of EGCs was further confirmed. Conclusions & InferencesEnteric glial cell activation can protect enteric neurons from damage due to diabetes in the acute stage of the disease, in part via the promotion of neurotrophin release.