Adipocyte tissue inflammation orchestrates the occurrence and development of diseases induced by obesity. Here, the effects of Lagerstroemia speciosa (L.) Pers total flavonoids (LTF) on TNF-α-induced insulin resistance (IR) and inflammatory response in 3T3-L1 adipocytes and underlying mechanisms were studied. Cell glucose uptake test confirmed that TNF-α could induce IR in 3T3-L1 adipocytes. The sensitivity of 3T3-L1 adipocytes to insulin was increased by LTF treatment. The phosphorylation of IRS1 and Akt in TNF-α-treated 3T3-L1 adipocytes was markedly restored by LTF treatment. The results revealed that interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) mRNA expression was elevated in TNF-α-administered 3T3-L1 adipocytes, whereas the mRNA expression of adiponectin (ADPN) was considerably decreased. When treated with 50 μg/mL LTF, the IL-6 and MCP-1 mRNA expression levels were drastically reduced, and the ADPN mRNA expression level was significantly raised. Moreover, the concentration of IL-6 in the supernatant of the medium was decreased after LTF treatment compared with the model group. Western blotting results showed that the phosphorylation of p38, JNK, and ERK of mitogen-activated protein kinase (MAPK) signaling pathways and IкB of NF-кB signaling pathway were inhibited. It suggested that LTF improves TNF-α-induced IR and inflammatory response in 3T3-L1 adipocytes via inhibiting MAPK and NF-кB signaling pathways.