OBJECTIVE - To determine the influence of insulin therapy on physical symptoms, emotional and general well-being, and treatment satisfaction in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - A descriptive prospective 2-year cohort study was performed. The study population consisted of 272 eligible NIDDM patients of Dutch origin ≥40 years of age who had a known diabetes duration ≥3 months and who were treated with diet and/or oral hypoglycemic agents. Dependent variables in the logistic regression analysis were scores on the Type 2 Diabetes Symptom Checklist, the Profile of Mood States, and questions regarding general well-being and treatment satisfaction. Potential determinants under study were age, sex, known diabetes duration, insulin dose, duration of insulin therapy, comorbidity, baseline and change in metabolic parameters and cardiovascular risk factors. RESULTS - A baseline and 2-year questionnaire were available for 157 patients (58%). During follow-up, 39 of them (24.8%) were treated with insulin. Initiation of insulin therapy was significantly associated with improved glycemic control (mean HbA(1c) 8.2 ± 1.4 [SD] to 7.4 ± 0.9%, P = 0.001) and weight gain (BMI 27.1 ± 3.9 to 28.6 ± 4.3 kg/m2, P = 0.000). Of all symptom and well-being scores, only feelings of emotional fatigue worsened significantly, although modestly (0.4-1.7 on a scale of 0.0-10.0, P = 0.02). Although diabetes management with insulin was experienced as more demanding (P = 0.04), treatment satisfaction scores were not adversely influenced (2.5- 1.9, P = 0.39). High insulin doses were significantly and independently associated with high symptom scores (total score, hypoglycemic score) and with low mood (displeasure score, anger, tension, emotional fatigue) and perceived state of health. CONCLUSIONS - Initiation of insulin therapy in type 2 diabetes improves glycemic control effectively, has little influence on physical and psychological well-being dimensions, and does not affect treatment satisfaction.