Propolis is a gelatinous mixture produced by honeybees for maintaining the structural integrity and aseptic environment of the hive. The bioactive compounds are crucial for the health effects of propolis. Given that propolis is generated by honeybees, its exact bioactives and health benefits are varied due to the sources of materials. Here we investigated whether propolis collected from Yaunqu County, Shanxi,China, potentially protected against mice intestinal damage-induced by dextran sulfate sodium (DSS). Our results indicated that propolis effectively alleviated DSS-induced intestinal injury and the mechanisms behind it involving in targeting macrophage inflammation including pro-inflammatory cytokines, pro-inflammatory signal pathways Nuclear Factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK), and tissue factors. This research enriches the evidence of propolis as a candidate for protection against intestinal injury.