Background: The aim of the study was to evaluate the relationship between serum cathelicidin level and diabetic nephropathy (DN) in patients with type 1 diabetes mellitus (T1DM). Methods: The study group consisted of 76 patients with T1DM (47 men), aged 36 ± 7 years, and with duration of T1DM 14 (7–18) years. Serum cathelicidin was measured by ELISA test in healthy controls (n = 20) and in 76 T1DM patients grouped as follows: G1 = patients with normal urinary albumin excretion (n = 20), G2 = patients with microalbumin excretion (n = 19), G3 = patients with macroalbumin excretion but normal serum creatinine level (n = 19), and G4 = patients with macroalbumin excretion with increased serum creatinine (n = 18). Results: There was no significant difference in serum cathelicidin levels between healthy controls and G1 diabetic patients, but serum levels were progressively increased from the stage of microalbuminuria to frank nephropathy (P < .001). Positive correlation between serum cathelicidin level and the presence of DN, thyroid‐stimulating hormone, total cholesterol, and negative with male sex and fasting plasma glucose, was found. In multiple regression analysis, serum cathelicidin level was associated with the presence of DN after adjustment of sex, waist‐to‐hip ratio, total cholesterol, and thyroid‐stimulating hormone. Conclusions: Patients with T1DM and DN are characterized by increased serum cathelicidin level. There was an independent relationship between serum cathelicidin level and DN. Serum cathelicidin level can be used as an early marker for the presence and progression of DN in T1DM patients.