Background: Obesity is a positive chronic imbalance between energy intake and expenditure mediated through leptin signaling pathway. Obesity is associated with increased incidence and mortality of cancer, including non-Hodgkin's lymphoma (NHL). Associations between polymorphisms in leptin and leptin receptor genes and non-Hodgkin's lymphomas have been reported. Aim of study: evaluate the impact of body mass index and serum leptin level on response of NHL patients to chemotherapy. Subjects and methods: 100 NHL adult patients were included. For each patient, body mass index was determined. Investigations performed include laboratory (complete blood count, serum levels of lactate dehydrogenase, liver enzymes, bilirubin, albumin, creatinine, uric acid, and lipid profiles, and serum leptin level), imaging (pelvi-abdominal ultrasonography, computerized tomography scans and positron-emission tomography), and pathologic examination of biopsy samples. Appropriate chemotherapy regimens were given for 6 cycles, and then the patients were re-assessed to determine their response to chemotherapy. Results: Positive correlation was observed between body mass index and serum leptin level. Serum leptin level was higher in non-Hodgkin's lymphoma patients presented with B symptoms compared to those without B symptoms. Body mass index and serum leptin levels were significantly higher in patients with stage-4 disease compared to those with stage-1. Also, body mass index and leptin levels were significantly higher in patients who did not respond to chemotherapy and showed progressive disease compared to those who showed regressive response. Conclusion: Increased body mass index and elevated serum leptin level had a worse impact on response of non-Hodgkin's lymphoma patients to chemotherapy.