This study aimed to examine the expression of cholecystokinin-1 receptor (CCK-1R) in the kidneys of type 2 diabetic nephropathy (DN) and the correlation of CCK-1R mRNA and proteinuria. Localization of CCK-1R in kidney of diabetic patient with nephropathy was examined by immunohistochemistry and in situ hybridization. The glomeruli did not express CCK-1R in either control or diabetic nephropathic kidneys. However, the expressions of CCK-1R protein and mRNA in tubules were significantly increased in DN, which had no relationship with the severity of DN. Furthermore, there was a positive correlation between the percentage of cells positive for CCK-1R mRNA and the degree of proteinuria. Increased CCK-1R expression could be demonstrated in the tubules and the CCK-1R might be implicated in the development of proteinuria in human DN.