Abstract： Objective To investigate whether a Ras homologue, Rhes, is expressed and the effect of efaroxan on Rhes expression in islet β cells. Methods Reverse transcription and polymerese chain reaction(RT PCR)was employed to detect Rhes transcript in clonal rat insulin releasing cells (RINm5F and BRIN BD11 cells) and intact isolated rat islets. Insulin release was measured after exposure to efaroxan and/or KU14R for 2hr under the condition that BRIN BD11 cells were precultured with or without efaroxna for 24 hr. Results (1) Rhes is expressed in RINm5F cells and BRIN BD11 cells and isolated rat islets. (2) Rhes expression was down regulated by efaroxan. KU14R, a structurally related molecule to efaroxan, had no effect on Rhes expression, however, it completely blocked the down regulation of Rhes expression induced by efaroxan. (3) Efaroxan induced a state of functional desensitization in clonal BRIN BD11 cells after 24 h exposure. (4)Unlike being in isolated human and rat islets, KU14R itself stimulated insulin secretion in clonal BRIN BD11 cells. Conclusion Rhes is expressed in islet β cells. Rhes represents an imidazoline regulated molecule that could be involved in mediating the insulin secretory response to efaroxan.