People with Type 2 diabetes (T2D) show dysregulated inflammatory responses to acute stress, but the effect of sex on inflammatory responses in T2D remains unclear. The purpose of this study was to investigate differences in interleukin (IL)-6 stress responses between older men and women with T2D. One hundred and twenty-one people (76 men; mean age = 64.09, SD = 7.35, 45 women; mean age = 63.20, SD = 6.70) with doctor-verified T2D took part in this laboratory-based stress testing study. Participants carried out acute mental stress tasks, and blood was sampled at baseline, immediately poststress, 45 min poststress, and 75 min poststress to detect plasma IL-6 concentrations. IL-6 change scores were computed as the difference between the baseline measurement and the three time points poststress. Main effects and interactions were tested using mixed model analysis of covariance. We found a significant main effect of time on IL-6 levels, and a significant Sex × Time interaction. In adjusted analyses including the three change scores and all the covariates, the significant Sex × Time interaction was maintained; IL-6 responses were greater in women at 45 and 75 min poststress compared with men, adjusting for age, body mass index, smoking, household income, glycated hemoglobin, oral antidiabetic medication, insulin/other injectable antidiabetic medication, depressive symptoms, and time of day of testing. Different inflammatory stress response pathways are present in men and women with T2D, with women producing larger IL-6 increases. The long-term implications of these differences need to be elucidated in future studies.