Euphorbia tithymaloides L., a native plant of tropical and subtropical areas in Asian countries which has been known as traditional medicine with a wide range of healing effects, such as anti-hemorrhagic, anti-diabetic, anti-bacterial, anti-inflammatory, and anti-tumor activity. The present study was orchestrated to evaluate the potential anti-inflammatory and anti-diabetic effects of Euphorbia tithymaloides ethanol extract (ETE). The anti-inflammatory and anti-diabetic activities were studied through the treatment of RAW 264.7 murine macrophages cells and 3T3-L1 adipocytes with various concentrations of ETE (50, 100, 200, and 400 mu g/mL). The results showed that ETE below 400 mu g/mL has no negative effect on RAW 264.7 cell proliferation. ETE decreased nitric oxide production in macrophages RAW 264.7 cell line and reduced the protein expression of cyclooxygenase 2, interlukin-6, inducible nitric oxide synthase, tumor necrosis factor-a and nuclear factor-kB in a dose-dependent manner. In 3T3-L1 preadipocytes, the increase of ETE concentration did not affect cell viability, but significantly enhanced adipogenesis through increase in differentiation and the expression of peroxisome proliferator-activated receptor gamma, CEBP alpha, glucose transporter type 4 and insulin receptor substrate 1. ETE also stimulated 2-NBDG uptake through activation of the insulin signaling pathway through insulin-sensitizing PPAR. agonists in a dose-dependent manner. In conclusion, our findings that ETE has immunomodulatory activity and anti-diabetic effects, which can be used for treating inflammation and type II diabetes.