Abstract: Objective: This study evaluated the efficacy of donkey-hide gelatin (Ejiao) in alleviating microcirculatory disorders in mice and explored its underlying mechanisms. Methods: Female ICR mice were randomly divided into four groups: Healthy control, model, Ejiao mid-dose (1.5 g/kg), and Ejiao high-dose (3 g/kg). A microcirculatory disorder model was established by injecting dextran into the tail vein. Real-time blood perfusion in the auricles was continuously monitored using a laser speckle flowmetry system. The number of functional capillaries was assessed under a stereomicroscope, and hemorheological parameters were quantified using a hemorheometer. Enzyme-linked immunosorbent assay was used to measure levels of vascular activity- and metabolism-related factors, neurotransmitters, hormones, and inflammatory cytokines to elucidate the potential mechanisms. Additionally, histopathological changes in the liver and kidneys were assessed. Results: In the mid-dose Ejiao group, auricular blood perfusion levels at 15 and 30 minutes increased significantly by 36.76% and 36.02%, respectively, compared to that at baseline (0 min) (P<0.01). Furthermore, at 30 minutes, both the mid- and high-dose Ejiao groups exhibited significant increases in the number of open capillaries by 34.61% and 38.46%, respectively, compared to that in the model group (P<0.01). Hemorheological analysis revealed that the model group had significantly elevated levels of whole-blood and plasma viscosity, hematocrit, and fibrinogen (P<0.05 or P<0.01), along with a reduced erythrocyte sedimentation rate (P<0.05). In contrast, the mid-dose Ejiao group showed significant improvement in these parameters (P<0.05). Both mid- and high-dose Ejiao treatments significantly decreased the level of plasminogen activator inhibitor-1 (PAI-1) (P<0.01) and markedly increased the level of 6-keto-prostaglandin F1α , a stable metabolite of prostacyclin (P<0.05), compared to that in the model group, suggesting a potential role of Ejiao in modulating vascular function. Additionally, both Ejiao-treated groups showed increased levels of Ca²⁺/Mg²⁺ ATPase and cyclic guanosine monophosphate, indicating that Ejiao might alleviate microcirculatory disorders by enhancing energy metabolism. The levels of the neurotransmitters acetylcholine and norepinephrine, as well as the hormones estradiol and luteinizing hormone, were closer to those of the healthy group in Ejiao-treated mice, indicating regulatory effects on neuroendocrine imbalances. Inflammatory factor analysis demonstrated that mid-dose Ejiao significantly reduced the levels of tumor necrosis factor-α and interleukin-1β (P<0.05), thereby mitigating inflammation associated with microcirculatory disorders. Histopathological observations further confirmed that Ejiao treatment alleviated tissue damage and promoted structural recovery in the liver and kidneys. Conclusion: Mid-dose Ejiao effectively alleviated microcirculatory disorders by modulating vascular activity, correcting metabolic imbalances, restoring neuroendocrine homeostasis, and suppressing inflammatory responses. These findings provide strong scientific evidence supporting the therapeutic potential of Ejiao for the treatment of microcirculatory disorders.