OBJECTIVE To evaluate the interrelationships between the rate of absorption of soluble insulin, SCBF, and anthropometry in normal subjects. METHODS In 12 normal men (age range 23-30 yr, BMI 18.2-41.3 kg/m2), simultaneous assessment of the absorption of 125I-labeled soluble insulin and SCBF (99mTc clearance) was performed, on separate study days, for the anterior abdominal wall, anterior midthigh, and the upper arm sites. Each site was examined in a randomized order on two separate occasions. Absorption of 125I-soluble insulin was determined by external monitoring of residual radioactivity levels at the injection site for 6 h postinjection. Residual radioactivity level-time curves, including the characteristic early phase of slow absorption of soluble insulin (the lag phase), were described using two- and three-parameter biexponential models. Anthropometric measurements included BMI, ultrasonic measurement of the subcutaneous adipose tissue layer, and caliper skin fold thickness at the anterior abdominal wall, biceps, triceps, anterior midthigh, and subscapular sites. RESULTS A highly significant positive relationship was observed between the rate of absorption of 125I-soluble insulin and SCBF (rS = 0.44-0.52; P < 0.01-0.001). The duration of the lag phase was inversely correlated with SCBF (rS = 0.34 - 0.51; P < 0.01-0.001). Inverse relationships also were observed for the subjects' degree of adiposity with the rate of soluble insulin absorption (rS = -0.43(-)-0.71; P < 0.001) and SCBF (rS = -0.27(-)-0.62; P < 0.05-0.001). Significantly shorter lag phase was observed for the abdominal site compared with thigh and arm injection sites (P < 0.05-0.01). CONCLUSIONS The rate of absorption of soluble insulin, including during the lag phase, is positively correlated with SCBF. Increasing adiposity prolongs the duration of the early lag phase and reduces the rate of absorption of soluble insulin and SCBF.