AIM: Peroxisome proliferator-activated receptor γ (PPAR γ) is a critical factor for some pathways that involve in adipogenesis and osteogenesis. The aim of study was to compare PPARγ gene expression, different cytokines' levels and bone markers in osteopenic and non-osteopenic obese subjects. METHODS: A total of 265 obese participants recruited in the current case-control cross sectional study. BMD at region of lumbar spine and hip were measured in all participants. We categorized all participants into two osteopenic and non-osteopenic groups. RESULTS: Of the 265 obese participants, 77 (29.05 %) were osteopenic and 188 (70.95%) were non-osteopenic. We found significantly higher concentration of crosslaps and IL6 and lower free fat mass in osteopenic group. The relative gene expression of PPAR γ in osteopenic group was significantly higher than non-osteopenic group. Based on relative gene expression tertiles participants were rearranged all participants into two new groups; low expressed PPAR γ with low PPAR γ gene expression≤75% and high expressed PPAR γ with PPAR γ gene expression>75%. The levels of fat percents, triglyceride, LDL, HDL and total cholesterol in high expressed PPAR γ group were significantly higher than low expressed PPAR γ group. Also, significantly higher concentration of IL10, IL6 and TNFα and lower concentration of hs-CRP were detected in high expressed group compare to low expressed PPAR γ group. The BMD, T-score and Z-score in high expressed PPAR γ group were lower than low expressed PPAR γ group. CONCLUSION: Our findings suggest that the over expression of PPARγ in obese individual's PBMCs may have a critical role in relationship between obesity and bone loss. Further studies recommended clarifying the mechanism of PPARγ in bone turnover in obese subjects.