Aim: To evaluate the relationship between serum levels of visfatin, lead (PB) and cadmium (Cd) in obese male subjects with osteoarthritis (OA). Methods: A total of 40 obese males (age: 25 -55 years; BMI ≥ 30) participated in the study. They were subdivided into 3 groups; group A, 10 patients with OA; group B, 15 workers in gasoline filling stations; group C, 15 obese subjects without any apparent other health problems or chronic diseases. After overnight fasting, blood samples were collected from all participants to evaluate blood levels of Pb, Cd and HbA1c, in addition to serum visfatin, lipid profile, glucose and total antioxidant state (TAS). Results: Obese patients with OA have significantly higher BMI value (p < 0.05) than the other groups. Obese gasoline station workers demonstrate highest blood lead levels compared to the other groups. Serum visfatin levels in obese subjects with OA were significantly higher than that reported in the other groups. Blood lead contents and serum visfatin levels were positively and significantly correlated in the three groups, and greatest correlation coefficient value (r) was reported in obese OA patients followed by obese gasoline station workers and healthy obese subjects, respectively. BMI in obese healthy subjects shows weak positive and non-significant relationship with serum visfatin levels, while highly positive and significant correlation was reported between these two markers in obese gasoline station workers. However, BMI values and serum visfatin showed weak negative and non-significant correlation with serum visfatin levels in obese OA patients. Conclusion: Serum visfatin levels could be key regulators of obesity and OA, and an important partner with excessive environmental exposure to Pb in the pathogenesis of these disorders.