Background/Aim. The importance of chronic inflamma-tion, endothelial dysfunction, certain cytokines, and se-lectins in the development of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) is increasing-ly evident and supported by evidence. However, the role of chronic inflammation in the development of diastolic dysfunction (DD) in the early stages of cardiomyopathy in T2DM patients is insufficiently studied. The aim of this study was to examine the possible association of interleu-kin (IL)-1β, IL-1α, IL-6, and E-selectin with DD in T2DM patients with still preserved ejection fraction (EF). Meth-ods. The research included a total of 74 subjects divided into two groups: a group with proven T2DM, i.e., diabetes group (DG) (n = 45), and a healthy control group (HCG) (n = 29). Echocardiographic parameters of DD and serum levels of IL-1β, IL-1α, IL-6 and E-selectin were compared between the two groups, and the correlation of echocar-diographic parameters of DD and serum biomarkers was examined in both groups. Results. Subjects with T2DM had significantly different values of DD parameters com-pared to HCG but also higher values of IL-6 (19 pg/mL vs. 12 pg/mL, p = 0.002), E-selectin (2,036 pg/mL vs. 1,522 pg/mL, p < 0.001), and IL-1α (46 pg/mL vs. 37 pg/mL, p = 0.003). The majority of subjects who met the echocardiographic criteria of DD were from DG. In subjects with proven DD, significantly higher values of IL-6 (20.5 pg/mL vs. 16 pg/mL, p = 0.003) and IL-1β (15.0 pg/mL vs. 11.4 pg/mL, p = 0.036) were verified com-pared to subjects without DD. Conclusion. The results of our study indicate the presence of a connection between chronic inflammation and echocardiographic parameters with the onset of DD in the phases of preserved cardiac EF in patients with T2DM.