Ginsenoside Re reduces insulin resistance in 3T3-L1 adipocytes and high-fat diet (HFD) rats through inhibition of JNK and NF-κB activation. Intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 20 mg/kg is lethal to mice, and 70% to 80% of the mice die within 60 h. However, pretreatment of the mice with Rg1 or Ginsenoside Re increases their survival rates in a dose-dependent manner. With the doses of Rg1 or Ginsenoside Re increase from 2.5 to 5 mg/kg, the survival rate is elevated from 60% to 90% (Rg1) or from 30% to 40% (Ginsenoside Re). All the mice administered Rg1 at a minimal dose of 10 mg/kg are protected from death compared to 80% survival of mice treated with an equal dose of Ginsenoside Re. To protect all the mice, 20 mg/kg Ginsenoside Re is needed. To investigate the anti-inflammatory potential of Rg1 and Ginsenoside Re, 1 mg/kg Rg1 or Ginsenoside Re is injected into rats and then challenged the animals with LPS. The injection procedure itself causes a transient stress-induced increase in body temperature of ~1.2°C in each group. Thereafter, LPS-challenged rats without pretreatment develope a robust biphasic fever, with the first peak reaching ~1.5°C at 2 h and the second peak reaching 1.8°C at 4 h. In contrast, the temperature changes for the Rg1-, Ginsenoside Re-, and TAK-242-treated groups are only 0.9, 1.2, and 0.8°C at 2 h and 1.3, 1.4, and 1.0°C at 4 h, respectively. Pretreatment with Rg1, Ginsenoside Re, or TAK-242 significantly attenuates LPS-induced alterations in body temperature.