Objective To study the effect of glucose change on expression of prepro orexin and its receptors, orexin 1 receptor (OX 1R) and orexin 2 receptor (OX 2R) in rat hypothalamus tissue and pancreatic islets cells. Methods The acute hypoglycemia rat model was induced by subcutaneous injection of insulin. The effect of 2 8 mmol/L and 8 3mmol/L glucose on pancreatic islet cell orexin system was detected in pancreas islet cell culture. The expression of prepro orexin and OXR mRNA was examined by reverse transcription polymerase chain reaction in rat hypothalamus tissue and pancreatic islets cell. Results Expression of orexin mRNA increased about 150% in insulin induced hypoglycemia rat hypothalamus tissue, compared to control group ( P <0 01), whereas expression of OX 1R mRNA decreased up to 30% ( P <0 01). However, expression of OX 2R mRNA did not show significant change in comparison with control group. The expression of prepro orexin mRNA increased up to 100% in rat pancreas islet cell cultured in 1640 medium with 2 8 mmol/L glucose, compared to 8 3mmol/L glucose after 6 h ( P <0 01). But the expression of OX 1R mRNA level was not sensitive to acute glucose fluctuation. Conclusions The orexin and OX 1R are stimulated by falls in plasma glucose and inhibited by signals related to feeding. Moreover, glucose plays a role in modulating the gene expression of prepro orexin in rat pancreatic islet cells.