BACKGROUND/OBJECTIVES: One of the major causes of hypertension (HT) is the transition of normal weight (NW) status to overweight (OW) status and obesity in a population, which leads to cardiovascular disease (CVD) and other disorders. A variety of factors/variables are involved in the development of HT and OW-related hypertension (OHT). However, we planned to investigate the pathophysiological role of serum leptin (Lep), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total cholesterol (TC) and serum testosterone (ST) in OHT in middle-aged men. METHODS: We consulted three groups of middle-aged men (age: 51-60 years)-an HT group (n: 97, high normal weight (HNW), body mass index (BMI): 23-24.9 kg/m RESULTS: Significant variations were obtained for the comparisons of TNF-α, Lep, ST and TC for the patient groups. OHT vs. NC showed a significant difference for ST. OHT vs. NC and OHT vs. HT had significant variations for IL-6. Significant changes were obtained for the serum levels of TNF-α, Lep, IL-6, ST and TC among groups. Significant and positive linear associations were obtained for TNF-α, Lep, TC and IL-6. Significant and negative linear associations were found for ST plotted against Lep, TNF-α and IL-6. CONCLUSIONS: The current report provides pathophysiological evidence of the interactive role of serum Lep, TNF-α, ST, TC and IL-6 in middle-aged men with HT and OHT. We suggest that the changes we noted in the present study would be helpful for further BMI-based studies in various subcategories of NW, OW and obese subjects with/without HT.