Inflammation is a hallmark of esophagitis. Rutaecarpine or rutecarpine is an alkaloid compound with both anti-inflammatory and anti-oxidative activity. Here, we sought to evaluate potential protective effects of Rutaecarpine on reflux esophagitis in a murine model of the disease, which was treated with different doses of Rutaecarpine (5, 10 and 20 mg/kg) and Omeprazole (20 mg/kg) for 6h, the results of which were compared with a non-esophagitis control group. Biochemical markers were measured based on tissue and serum samples collected from esophagitis-positive and control animals. Rutaecarpine significantly reduced macrophage cell viability, while negatively regulating nitric oxide (NO) and inducible NO synthase (iNOS), interleukin-1beta (IL-1β), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE₂). Rutaecarpine treatment was associated with marked reversal of esophageal lesions, reduced gastric secretion and activity (P<0.001), increased gastric pH and SH groups, as well as reduced levels of H₂O₂, free iron, calcium (P<0.001). Additionally, Rutaecarpine treatment negatively regulated the expression of H⁺K⁺ATPase and histamine, while markedly altering the levels of lactoperoxidase (LPO), catalase (CAT), superoxide dismutase (SOD) glutathione (GSH) and monocyte chemoattractant protein-1 (MCP-1) (P<0.001). Rutaecarpine was found to confer protective effects against esophagitis in rats.