Our primary objective was to assess changes in quality of life (QOL) associated with changes in insulin regimen in patients with type2 diabetes mellitus. Secondary objectives were to assess the reasons for and patterns of changes in insulin regimen, and the effects on glycemic control. This 12-week, observational study included patients with type2 diabetes mellitus (n=625) who planned to change insulin regimen (type of insulin, injection device and/or number of injections). The primary outcome measure was a change from baseline in QOL assessed by the Insulin Therapy-Related (ITR) QOL questionnaire. The secondary outcome measures included change from baseline in plasma glycated hemoglobin (HbA1c) level, the reasons for and pattern of insulin regimen change, and change from baseline in QOL assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ). QOL did not worsen during the study. Improvements were seen in the ITR-QOL 'daily activities' subscale score (baseline: 12.7±2.3; week12: 12.9±2.3; P=0.038, n=568) and the DTSQ 'perceived frequency of hyperglycemia' subscale score (baseline: 3.4±1.6; week12: 3.0±1.7; P<0.001, n=573). Glycemic control improved, as evidenced by decreased plasma HbA1c levels (baseline: 8.21±1.47%; week12: 7.85±1.31%; P<0.001, n=606). It was suggested that insulin regimen changes might improve glycemic control in Japanese patients with type2 diabetes mellitus without worsening QOL. This trial was registered with ClinicalTrials.gov (no. NCT01055808).