Insulin resistance in type 2 diabetes subjects was investigated before and 6 months after insulin administration in 43 type 2 diabetes patients (28 females and 15 males). Their age was 56.1+/-8.6 years, diabetes duration 11.7+/-6.8 years, BMI 29.5+/-5.3 kg/m2. All patients were on maximal dosage of oral hypoglycaemic agents and had poor metabolic control (HbA1c 11.2+/-1.6%). Insulin sensitivity was measured by euglycaemic clamp (insulin infusion rate 1 mU kg-1 min-1). The glucose disposal rate (M-value) was considerably lower in patients (2.4+/-1.6 mg kg-1 min-1, 0.2-8.1) compared with healthy subjects (7.1+/-0.2 mg kg-1 min-1, p<0.01). M-value was strongly associated with WHR (r=-0.41, p<0.05). The patients with poorest insulin sensitivity had the highest level of total cholesterol (r=-0.41, p=0.02) and LDL-cholesterol (r=-0.38, p=0.03). After 6 months of insulin treatment BMI was 30.3+/-4.2 kg/m2 (p<0.05), mean weight increase was 2.7+/-0.8 kg. M-value was substantially increased to 4.5+/-2.3 mg kg-1 min-1 (p<0.001), the degree of improvement depended on basal insulin sensitivity (r=-0.55, p<0.01). HbA1c was reduced to 7.7+/-1.4% (p<0.01), the correlation M-value with change of HbA1c (r=-0.59, p<0.01) was shown. Total cholesterol decreased from 6.3+/-1.1 to 5.4+/-1.1 mmol/l, LDL-cholesterol from 4.1+/-1.1 to 3.4+/-1.0 mmol/l, triglycerides from 2.6+/-1.6 to 1.6+/-0.7 mmol/l (p<0.001). In conclusion, insulin treatment of type 2 diabetes patients leads to decrease in insulin resistance due to reduction in glucose toxicity and plasma atherogenicity despite weight gain.