Snakebite by Deinagkistrodon acutus often leads to severe tissue necrosis, hemorrhage and inflammation due to the high content of metalloproteinase (SVMP) and phospholipase A2 (PLA2). These impairments can be significantly alleviated by serum of Sinonatrix annularis, a nonvenomous snake endogenous in China. Here, the proteome alteration of envenomed mice were determined using TMT labeling technique to clarify the mechanism of D. acutus envenomation and S. annularis protection.