Aim: The accumulation of free fatty acids in non-adipose tissues lead to cellular lipotoxicity and induce endoplasmic reticulum (ER) stress. To restore ER homeostasis, cells evoke an adaptive mechanism that is known as the unfolded protein response (UPR). The aim of this study was to investigate the potential relationship between ER stress and some inflammasome complexes under lipotoxic ER stress conditions in the mouse macrophage cell line (RAW 264.7). Materials and Methods: The mouse macrophage cells (RAW 264.7) were treated with Ethanol-BSA (control) or Palmitate-BSA (500μM). The expression of inflammation-related target genes was investigated using the qRT-PCR method. Results: A significant induction at the mRNA levels of mTNFα, mNFκBIB, mIRF7, mCCL5, and reduction at the mRNA level of mIRF1 after lipid-induced metabolic ER stress were observed in RAW 264.7 cells. Conclusion: Together, these findings confirm that UPR regulates the expression of key inflammation-related genes under saturated lipid-induced stress conditions.