Administration of somatostatin to rats induced a transient reduction of serum levels of deoxyribonuclease I (DNase I) activity in a dose-dependent manner, followed by a substantial decrease of DNase I activity in the lower gut. Activity in the parotid gland, liver, and kidney did not change. Real-time PCR analysis of the DNase I gene transcript in ileum indicated that the decrease was due to down-regulation of gene expression. Based on these responses, rat tissues expressing DNase I could be classified into two types, somatostatin-sensitive and somatostatin-resistant, and the level of DNase I activity in the lower gut seems to be controlled by somatostatin.