In order to investigate how glucocorticoids affect the expression of secretory leukocyte peptidase inhibitor (SLPI), which is overexpressed in a variety of cancers, clobetasol was added to cell culture medium of U937 cells and the SLPI mRNA levels were examined. The in vitro effect of the treatment on SLPI expression was detected by reverse transcriptase-polymerase chain reaction. Clobetasol treatment of U937 cells induced an up- and down-regulation of SLPI expression in a dose-dependent manner. Western blotting confirmed the down-regulation of SLPI protein expression. We hypothesized a loop formation in the SLPI genome domain, in which the glucocorticoid receptor regulates bi-directional transcriptional activity.