Kukoamine A (Kuk A) is a naturally occurring bioactive spermine alkaloid found in the root bark of Lycium chinense, and it exerts various therapeutic effects including antioxidant, neuroprotective, anti-inflammatory, and antidiabetic effects. This study evaluated the anti-inflammatory properties of Kuk A against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells and carrageenan-induced paw edema in rats. Pretreatment of cells with Kuk A significantly inhibited the production of reactive oxygen species, nitric oxide, prostaglandin E-2, cyclooxygenase-2 activity, tumor necrosis factor-alpha, interleukin-1 beta (IL-1 beta), and IL-6 in LPS-treated cells. In addition, pretreatment of rats with Kuk A significantly decreased inflammatory response to carrageenan-induced paw edema by alleviating proinflammatory cytokines in the serum, malondialdehyde levels in the liver and increasing the activities of liver antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) of carrageenan-treated rats. These results suggest the protective role of Kuk A in acute inflammatory reaction and could be useful in the treatment of inflammatory-related disorders.