Background: Obesity and insulin resistance elevate plasma leptin, while it lowers plasma levels of soluble leptin receptors (sOB-R). Objectives: To measure the levels of sOB-R in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and compare it to healthy controls. The study also aimed to investigate the influence of metformin on the levels of sOB-R in patients with T2DM and MetS. Materials and methods: A cross-sectional study was conducted on 66 participants (33 patients and 33 controls). Patients were divided into two groups; Group I included 17 newly diagnosed T2DM patients, and Group II included 16 patients with MetS. Patients were studied before and 3 months after treatment with 850 mg metformin treatment. Group III included 33 non-obese healthy individuals as a control group. Measurements such as height, weight, waist circumference, hip circumference, blood pressure examination, and biochemical tests including fasting blood sugar, HbA1c, total cholesterol (Ch), triglyceride, high-density lipoprotein (HDL), insulin level, plasma sOB-R levels were performed. Ch/HDL ratio, non-HDL cholesterol, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Waist Hip Ratio (WHR), and Body Mass Index (BMI) were calculated.Results: No statistically significant difference was found among the groups regarding sOB-R levels initially, but after metformin treatment, T2DM patients showed a significantly higher level (10.19 ng/ml). There was a significant increase in the levels of sOB-R after metformin treatment, as it increased from 7.82 ng/ml to 10.19 ng/ml in T2DM, and from 6.92 ng/ml to 7.82 ng/ml in MetS patients. Conclusion: Metformin significantly increases the plasma levels of sOB-R in T2DM patients but only slightly increases these levels in MetS patients.