Objective<p>The aim of this study was to examine the fluctuations in CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and natural CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>T-regulatory (Treg) cells following an oral glucose tolerance test (OGTT) in participants with and those without type 2 diabetes (T2DM).</p>Methods<p>19 Japanese participants with T2DM (DM group) and 21 participants without diabetes (non-DM group) were recruited and underwent a 75-g OGTT. The cell numbers of leukocytes, lymphocytes, and the T cell compartment, such as CD4<sup>+</sup>, CD8<sup>+</sup>, and Treg, were calculated for blood samples obtained after an overnight 12 h fast and during a 75-g OGTT at 60 and 120 min.</p>Results<p>Before glucose loading, no differences in the cell numbers of leukocytes, lymphocytes, CD4<sup>+</sup>, CD8<sup>+</sup>, and Treg were observed between the DM group and the non-DM group. The proportion of CD8<sup>+</sup> was significantly reduced, whereas the proportion of CD4<sup>+</sup> was significantly increased, after 120 min of glucose loading in both groups. The proportion of Treg was not affected. Furthermore, a significant positive correlation was observed between the AUC<sub>0–120 min</sub> of CD8<sup>+</sup> and the change in the free fatty acid level following the OGTT (ρ = 0.39, P < 0.05), but not that of glucose or insulin.</p>Conclusion<p>The proportion of CD4<sup>+</sup> T cells was increased and that of CD8<sup>+</sup> T cells was reduced after glucose loading in both subjects with and without diabetes. These findings suggest that glucose loading dynamically affects the balance of the circulating T lymphocyte subset, regardless of glucose tolerance.</p>