Background <p>Endocan is a soluble proteoglycan containing dermatan sulfate is primarily produced by activated endothelium cells. Conflicting studies have not revealed an association between endocan and diabetic nephropathy (DN). The study aimed to assess the associations of endocan levels with glycemic and inflammatory indices in patients with type 2 diabetes mellitus (T2DM) and DN.</p> Methods <p>This study included 88 participants; of whom 30 had T2DM, and 30 patients had DN compared with 28 apparently healthy controls. Endocan levels were measured using an ELISA kit. Fasting insulin level was measured using a LIAISON chemiluminescent immunoassay. Glycated hemoglobin (HbA1c) was measured via CLOVER A1c Plus, and fasting blood glucose (FBG) was measured using colorimetric/enzymatic methods. Insulin resistance (IR) was determined via the HOMA-IR calculator. The glycemic indices were calculated as follows: glucose /insulin ratio G/I, quantitative insulin sensitivity check index (QUICKI), McAuley index (MACi), and triglyceride glucose (TyG) index. The systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) were calculated after CBC measurements.</p> Results <p>Endocan levels in patients with DN were significantly greater (<i>P</i> &lt; 0.05) than those in the control group. The FBG, HbA1c%, insulin, HOMA-IR, and QUICKI indices in the DN patients were significantly greater than those in T2DM patients and controls. The endocan level in DN group showed a negative correlation with TyG index (<i>r</i> = -0.355, <i>P</i> = 0.045) and HbA1c (<i>r</i> = -0.387, <i>P</i> = 0.035).</p> Conclusions <p>Endocan may play a role in the pathogenesis and development of DN and could be used as an effective therapeutic target.</p> Trial registration <p>Not applicable.</p>