Background and Aims Adhesive intestinal obstruction (AIO) is a type of mechanical bowel obstruction caused by abdominal or intestinal adhesions, and its onset and progression are closely associated with impaired intestinal mucosal barrier function. Danshen injection, a commonly used traditional Chinese medicine preparation with properties of promoting blood circulation and removing blood stasis, has shown therapeutic potential in various gastrointestinal diseases by improving microcirculation and promoting vasodilation. However, its specific mechanism of action in AIO remains unclear. This study was conducted to investigate the effects and potential mechanisms of Danshen injection on intestinal mucosal barrier function in a rat model of AIO.Methods Forty rats with experimentally induced AIO were equally randomized into four groups: the model group (receiving intraperitoneal saline) and three Danshen-treated groups administered low, medium, and high doses of Danshen injection (1, 2, and 4 mL/kg, respectively), once daily for 7 consecutive d. An additional 10 healthy rats received saline injections in the same manner and served as the normal control group. After the final intervention, all rats were euthanized under anesthesia. Hematoxylin and eosin (HE) staining was performed to evaluate the histopathological morphology of small intestinal tissues. Levels of D-lactic acid and endotoxin in peripheral blood were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mucin 2 (MUC2), mucin 3 (MUC3), and human defensin 5 (HD5)—key components of the intestinal mucus layer and innate immune response—were analyzed using quantitative real-time PCR (qRT-PCR). Colorimetric assays were conducted to assess oxidative stress markers in intestinal tissue, including nitric oxide synthase (NOS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Western blot was used to determine the protein expression levels of endogenous antioxidant pathway components: nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1).Results HE staining showed no significant histological changes in the intestinal tissues of the normal control group, with a mucosal injury score of 0. The model and treatment groups exhibited varying degrees of villous disorganization and tissue edema, with injury scores of 4.69±0.62, 3.36±0.41, 2.29±0.22, and 1.53±0.14 in the model, low-, medium-, and high-dose groups, respectively (all P<0.05 vs. model group). Compared with the normal control group, the other groups showed significantly increased levels of D-lactic acid and endotoxin in the blood (all P<0.05); elevated expression of MUC2 and MUC3, reduced HD5 expression (all P<0.05); increased NOS and MDA levels, decreased SOD and GSH-Px levels (all P<0.05); downregulated expression of Nrf2, HO-1, and NQO1 proteins in intestinal tissues (all P<0.05). These changes were significantly attenuated in the Danshen-treated groups in a dose-dependent manner (all P<0.05).Conclusion Danshen injection can alleviate intestinal mucosal injury in AIO rats, possibly by activating the Nrf2/HO-1/NQO1 signaling pathway and reducing oxidative stress, thereby enhancing the intestinal mucosal barrier function.