The purpose of this study was to assess whether laughter influences the expression of the receptor gene for prorenin that participates in the progression of diabetic nephropathy.Sixteen normal subjects and 23 patients with type 2 diabetes [12 nephropathy (-) and 11 nephropathy (+)] were recruited to examine the effects of laughter on the modulation of prorenin receptor gene expression. After watching a comedy show, laughter-induced changes in the levels of blood prorenin and the expression of prorenin receptor gene were analyzed by an antibody-activating direct enzyme kinetic assay and by reverse transcriptase polymerase chain reaction, respectively.In diabetic patients, laughter decreased the level of blood prorenin [93.4-60.4 ng/l in nephropathy (-) patients, 196.6-166.7 ng/l in nephropathy (+) patients] and up-regulated the prorenin receptor gene [1.49-fold in nephropathy (-) patients, 1.46-fold in nephropathy (+) patients]. No significant changes in the expression of this gene were recognized in normal subjects.The beneficial effects of laughter on preventing the exacerbation of diabetic nephropathy are strongly suggested in terms of normalizing the expression of the prorenin receptor gene followed by reducing the level of blood prorenin.