Abstract: Objective To examine the role of long chain fatty acids and GPR120 on adipocytes inflammation, endoplasmic reticulum stress and insulin signaling molecules. Methods We cultured 3T3-L1 pre-adipocytes, using 1 μM dexamethasone, 1μg/ml insulin and DMEM medium 10% fetal bovine serum inducted differentiation of 3T3-L1 adipocytes. After 2 h100 Μm PA stimulation, use western blot method to detect GPR120, XBP1 S, PERK, P-PERK, IRE-1α, P-IRE-1α, IKKβ, p-IKKβ, JNK1, P-JNK1, JNK2 and P-JNK2 protein expression levels. Add DMEM medium containing 100 ng/ml insulin, incubate 15 min, and use western blot method to detect IR, P-IR, IRS-1, p-IRS, Akt and P-Akt protein expression levels. Results Under the stimulation of PA, GPR120, XBP1 S, PERK, P-PERK, IRE-1α, P-IRE-1α, IKKβ, p-IKKβ, JNK1, PJNK1, JNK2 and P-JNK2 expression significantly increased (P < 0. 05), IR, P-IR, IRS-1, p-IRS-1, Akt and P-Akt protein levels decreased significantly (P < 0. 05), while using GPR120 LGW9508 blockers can inhibit this process. Conclusion Long chain saturated fatty acids can increase PA GPR120 protein expression, and induce fat endoplasmic reticulum stress response, inflammation and insulin resistance.