To investigate the relation between secondary hyperparathyroidism (SHPT) and insulin sensitivity, 15 subjects with SHPT (serum PTH >6.4 pmol/l, serum calcium <2.40 mmol/l, and normal serum creatinine) and 15 control subjects were investigated with an oral glucose tolerance test (OGTT) and a 3-h hyperglycemic clamp. Body composition was measured with dual-energy X-ray absorptiometry. No differences were found between the SHPT and control groups on any indices of glucose or insulin metabolism. However, when dividing the 30 subjects in the upper and lower halves according to serum 25-hydroxyvitamin D levels (<59 and >58 nmol/l), those in the lower half had significantly higher 2-h serum insulin value at the OGTT, significantly higher insulin secretion during the last hour of the clamp, and significantly lower insulin sensitivity index (ISI; glucose infusion rate/insulin secretion during the last hour of the clamp). In a multiple linear regression analysis correcting for age, gender, and body mass index (BMI), the serum 25-hydroxyvitamin D level was significantly and positively associated with the ISI. The amounts of total body and truncal fat were negatively and significantly associated with the ISI, whereas no association between measures of lean body mass were associated with insulin secretion or sensitivity.