AIM: Rheumatoid arthritis (RA) is an autoimmune disease that is marked by inflammatory response. PNPLA2 (phospholipase patatin-like) which encodes ATGL (adipose triglyceride lipase) also been identified as playing in inflammation. G0S2 (G0/G1) switch gene has been identified as one of the selective inhibitors of ATGL. PNPLA2 and G0S2 may be factors that can help predict the relationship between molecules affecting inflammation, as well as identify inflammatory pathways through genes involved in the metabolic pathway. METHODS: In the present study, we analyzed the expression levels of PNPLA2 and G0S2 genes as well as their protein concentrations by real-time PCR and immunoassay, respectively on 60 peripheral blood mononuclear cells (PBMC) which are included into 3 different groups of new case patients with RA, chronic patients with RA, and the control individuals. Also, to obtain more accurate information and results, the synovial fluid, triglyceride, cholesterol, and ESR levels were also analyzed. Statistical analysis was then performed with the software SPSS-18. RESULTS: PNPLA2 gene expression level was significantly increased in the newly diagnosed patients and the chronic RA patients in compared to the control group. Also, the serum levels of ATGL in the newly diagnosed patients and the chronic RA patients were significantly reduced compared to the control group. The gene and protein levels of G0S2 in the newly diagnosed patients elevated compared to other groups, but interestingly this increase in PBMCs was not significant. CONCLUSIONS: This is predicted that PNPLA2 gene expression in PBMCs is not only regulated by G0S2 gene, but different regulatory factors can also affect the expression level of this gene in the immune cells.