Inflammation caused by obesity, particularly in adipose tissue and the liver, can lead to insulin resistance (IR) and trigger type 2 diabetes mellitus (T2DM). It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation. Here, we report that isobavachromene (IB), a flavonoid derived from Psoralea corylifolia Linn., ameliorates IR in 3T3-L1 adipocytes by inhibiting the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the phosphoinositide 3-kinase (PI-3K)/protein kinase B (Akt) signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100 μmol/L. Additionally, IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages, as well as the phosphorylation levels of key proteins (NF-κB p65, extracellular-signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal kinase (JNK), and mitogen-activated protein kinase 38 (p38)) in the NF-κB and MAPK signaling pathways. In summary, IB improves glucose uptake in IR adipocytes, activates the PI-3K/Akt signaling pathway, inhibits the JNK and NF-κB inflammatory signaling pathways, and reduces adipocyte inflammation, thereby improving of IR in 3T3-L1 adipocytes.