Objective:To investigate the role of nitric oxide(NO) on the motility function of proximal colon of diabetes mellitus mice. Methods:The distribution and expression of nNOS in the proximal colon of diabetes mellitus mice were examined by fluorescence microscopy and Western-blotting, respectively. The effect of NO precursor L-arginine(L-Arg), nNOS inhibitor 7-nitroindazole(7-NI ),iNOS Amino guanidine(AG) on the proximal colon muscle strips muscular contractions were monitored by MD-2000 system. Results:The expression of nNOS in the proximal colon was up-regulated in DM group. L-Arg decreased the proximal colon muscle strips contractile tension, 7-NI increased the muscle strips contractile tension while AG had no effect. All drugs had no influence on muscle strips contractive frequency. Conclusion:Increased expression of nNOS is demonstrated in the proximal colon of diabetes mellitus mice, and NO may play an important role in the pathogenesis of diabetic proximal colonic dysfunction.