<jats:p>Plasma and liver SerpinB1 levels are elevated in mice with insulin resistance and promote β-cell proliferation in human islets. We measured serum SerpinB1 levels in Japanese subjects with or without type 2 diabetes (T2DM). We enrolled 12 normal glucose tolerance (NGT) and 51 T2DM subjects. There was no difference in serum SerpinB1 levels between the 2 groups (T2DM, 1.3 ± 0.9 ng/mL <jats:italic>vs</jats:italic>. NGT, 1.8 ± 1.7 ng/mL; <jats:italic>P</jats:italic> = 0.146). After adjusting for age and sex, the serum SerpinB1 levels were positively correlated with HOMA2-%S (β = 0.319, <jats:italic>P</jats:italic> = 0.036), and negatively correlated with fasting blood glucose (β = -0.365, <jats:italic>P</jats:italic> = 0.010), total cholesterol (β = -0.396, <jats:italic>P</jats:italic> = 0.006), low-density lipoprotein (LDL) cholesterol (β = -0.411, <jats:italic>P</jats:italic> = 0.004), triglycerides (β = -0.321, <jats:italic>P</jats:italic> = 0.026), and γGTP (β = -0.322, <jats:italic>P</jats:italic> = 0.026) in subjects with T2DM. Thus, circulating SerpinB1 is possibly associated with insulin sensitivity and better blood glucose level in Japanese subjects with T2DM.</jats:p> <jats:p><jats:bold>Trial registration:</jats:bold> UMIN Clinical Trials Registry, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=UMIN000020453" xlink:type="simple">UMIN000020453</jats:ext-link>.</jats:p>