Studies have reported that scorpion toxins have excellent anti-cancer effects; however, the antiinflammatory activity of scorpion peptides has rarely been studied. Here, a series of Mesobuthus martensii Karsch peptides (MMKPs) were isolated and the amino acid sequence was identified. The MMKPs mitigated TNF-a-mediated inflammation in human umbilical vein endothelial cells (HUVECs). The results showed that MMKP-1 (His-Glu-Gly-His) treatment (43.0 mM) significantly attenuated the reactive oxygen species (ROS) generation and mitochondrial membrane potential collapse in HUVECs. Moreover, MMKP-1 down-regulated the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions and blocked the NF-kB pathway to alleviate the damage caused by TNF-a. Of note, our study provides a good reference for the anti-inflammation research on scorpion oligopeptides.