We monitored the change in plasma ANP and BNP levels (as markers for left ventricular dysfunction (LVD)) in DM2 patients treated with pioglitazone (Pio) for 4 weeks. Thirty DM2 patients with no sign of heart failure were treated with Pio (15 mg/day), and their plasma ANP (normal levels <or=43 pg/ml) and BNP levels (normal levels <or=18.4 pg/ml) were examined. We also examined those levels in no drug-treatment group (n = 10) as well as buformine treatment group (n = 10). Among these groups, there were no significant differences in clinical profiles related to DM control. Pio treatment was terminated when BNP (above 100 pg/ml) and ANP levels (above 50 pg/ml) suggested the left ventricular dysfunction (LVD). The patients (n = 12) whose BNP levels reached to the LVD-positive levels showed the basal BNP levels above the normal upper limit (18 pg/ml), while the rest of subjects (n = 18) whose basal BNP levels within normal limits did not showed the LVD-positive levels in the Pio-treatment. On the other hand basal ANP levels did not predict the development to LVD. In conclusion, BNP levels are suggested to be a good marker of Pio-induced LVD, and the Pio treatment of DM2 patients with BNP levels above the normal limit should be carefully carried out by monitoring BNP levels.