Herein, first, we present the clinical data showing that obesity is a positive modulator of IL-8 and MCP-1, and next, we demonstrate in vitro that the ROS/TNF-α crosstalk promotes the expression of IL-8 and MCP-1 in human monocytic THP-1 cells through the mechanisms involving endoplasmic reticulum (ER) stress, stabilization of hypoxia-inducible factor (HIF)-1α, and activation of the nuclear factor(NF)-κB and extracellular signal-regulated kinase (ERK)-1/2 signaling pathways. This evidence concerns the gene CCL2 and obesity disorder.