Leptin is a highly pleiotropic adipokine. Pancreatic adenocarcinoma (PA) and leptin relationship is important. Our aim was to investigate the serum levels of leptin in patients with PA, the relationship of leptin with tumor progression and known prognostic parameters and its diagnostic, predictive and prognostic role.Thirty-three patients with PA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum leptin levels were determined using enzyme-linked immunosorbent assay (ELISA). Age, sex, and body mass index (BMI) matched to 20 healthy controls were included in the analysis.The median patient age at diagnosis was 59 years (range 32-84) and 20 (61%) patients were men. The tumor was located in the head of pancreas in 21 (63%) patients. The most common metastatic site was liver in 23 patients with metastasis (N=19; 83%). The median follow-up time was 26.0 weeks (range 1.0-184.0). At the end of the observation period, 32 patients (97%) had died. The baseline serum leptin levels were significantly higher in patients with PA than in the control group (p=0.02). Thirty-nine percent of 23 metastatic patients who received palliative gemcitabine-based chemotherapy (gCTx) were gCTx-responsive. Serum leptin levels were significantly higher in the gCTx-unresponsive patients compared with gCTx -responsive (median 5.32 vs 1.16 ng/mL, p=0.004). Conversely, serum leptin concentration was found to have no prognostic role on survival (p=0.20).Serum leptin levels may be a good diagnostic and predictive tool on the response to gCTx in PA patients.