MiRNA-146a is overexpressed in psoriasis. MiRNA-146a and miRNA-146b have partially overlapping functions. We evaluated blood miRNA-146a/b expression by syber green real time-PCR in psoriasis and in response to mono-therapy using narrow-band ultraviolet B (NB-UVB) phototherapy or methotrexate (MTX), and evaluated if they are possible biomarkers for disease activity and for response to NB-UVB and MTX therapies.. MiRNA-146a/b expression significantly increased in psoriasis patients before therapy than in the controls. However, miRNA-146a expression showed significantly higher fold increase than miRNA-146b. Moreover, miRNA-146a/b expression levels before therapy were significantly higher in the MTX group than in the NB-UVB group, which coincided with the higher PASI score in the MTX group before therapy. In addition, miRNA-146a/b expression significantly decreased in response to both therapies. The fold decrease after MTX therapy relative to before MTX therapy was significantly higher than that after UVB therapy relative to before UVB therapy, which coincided with the significantly higher reduction effect of MTX on the PASI score. Only miRNA-146a significantly and positively correlated with PASI score. In conclusion, miRNA146a/b expression levels are increased in psoriasis and decreased in response to psoriasis therapy and may be used in predicting the response to NB-UVB therapy or methotrexate. Also, miRNA-146a may be used as a biomarker for disease activity.