Background Endotrophin is one of the extracellular matrix proteins secreted by adipose tissue. In this study, we aimed to investigate the effects of changes in blood glucose levels on serum endotrophin levels secreted by adipose tissue and thus on diabetes. Methods In this prospective pilot study included 78 patients with type 2 diabete (T2D) with hemoglobin A1c level > 9 %. Lifestyle changes were recommended and appropriate medical treatment was initiated to all patients in order to reach the target HbA1c level. Data of anthropometric measurements, urinary albumin creatinine ratio (UACR), serum lipid parameters and endotrophin were collected in patients; all examinations were repeated after 3 months. Analysis was performed using Paired-Samles T test and Spearman tests. Results Of patients, 23 were female (54.8 %) and 19 were male (45.2 %). Mean age was 55.2 years, with mean diabetes age of 8.14 +/- 5.35 years. After 3 months follow-up, HbA1c, fasting glucose, C-reactive protein(CRP), UACR and endotrophin levels were observed to clearly reduce. The variation in serum endotrophin levels examined at the start of the study and in the 3rd month was identified to have a positive correlation with the variation in HbA1c and UACR levels (r = 0.342, p = 0.02; r = 0.484, p = 0.001). Multiple linear regression analysis showed percentage variation values (delta)-endotrophin levels were only independently correlated with (delta)-UACR (model r(2) = 0.257, p value = 0.00). Conclusions Endotrophin levels decreased significantly with the decrease in HbA1c. Unexpectedly, this reduction in endotrophin levels is closely related to the decrease in UACR, regardless of blood glucose regulation. We think that studies targeting endotrophin will contribute to the diagnosis, treatment and follow-up of diabetic nephropathy in the future.