In type II diabetes mellitus the altered hormonal state after menopause may represent an additional cardiovascular risk factor. Estrogen replacement therapy (ERT) is associated with a decreased cardiovascular risk, at least in nondiabetic post-menopausal women. We studied the effect of ERT on plasma lipids and lipoproteins and on LDL oxidation in 40 postmenopausal women with type II diabetes but with minimal vascular complications in a randomized placebo-controlled trial. Twenty patients were treated orally with 2 mg/d micronized 17β-estradiol and 20 patients with placebo for 6 weeks. Plasma total cholesterol (-6%, P=.04), LDL cholesterol (-16%, P=.0001), and apoB (- 11%, P=.001) levels decreased and HDL cholesterol (20%, P=.0001) and apoA-I (14%, P=.0001) levels increased after ERT compared with placebo. Glycated hemoglobin (HbA1c) decreased significantly after ERT (-3%, P=.03), the cholesterol content of the LDL particles decreased (-5%, P=.006), triglyceride content increased (16%, P=.01), and LDL particle size did not change significantly. ERT had no effect on parameters of LDL oxidation. We conclude that plasma levels of HDL cholesterol, apoA-I, LDL cholesterol, apoB, and glycated hemoglobin are improved in postmenopausal women with type II diabetes mellitus after treatment with 17β-estradiol, indicative of a better metabolic control, and that ERT has no effect on LDL oxidizability.