Objective:To investigate the relationship between the expression of nNOS-HO-2 and the high contration glucose treatment in the interstitial cells of cajal(ICC) in vitro. Methods:The ICC was isolated from the proxinal colon in newborn rats,and divided into control group,high glucose group and mannitol(osmolarity control) group. Cells viability was assessed by the MTT assay,and the morphologic changes of ICC was observed under microscopy. The expression of nNos and HO-2 was evaluated by Western-blotting. Results:Compared to the controls,high glucose markedly decrease the cell viability. After treatment of high glucose,most of the ICC lost their network of each other,and the expression of nNOS and HO-2 was also decreased. In mannitol treatment ICC,there was no changes in cell viability,cell morphology and nNos and HO-2 compared to the control cells. Conclusion:High glucose treatment could induce ICC cell damage and inhibit the expression of nNos and HO-2. The abnormal expression of nNos and HO-2 may play an important role in the intestines dysfunction of diabetic mellitus.