This study aims to investigate the therapeutic effect of Paeoniae Radix Alba (PRA) on intestinal mucosal microcirculation disturbance in ulcerative colitis (UC) rats, and to explore the mechanism of PRA in the treatment of UC. Forty male SD rats were randomly divided into the normal control group, model group, mesalazine group (0.42 g/kg) and PRA low-dose and high-dose groups (0.5, 2.0 g/kg). The UC rat model was induced by 5% dextran sulfate sodium dissolved in drinking water for seven days. After successful modeling, the UC rat model was given intragastric administration for seven days. During the experiment, the general condition and the body weight were recorded. The colonic mucosal microcirculation was observed by laser speckle imaging. The histopathologic changes of colon were observed by HE staining. ELISA assay was performed to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-4, IL-10 in serum and colonic tissues, as well as the serum levels of platelet activating factor (PAF) and tissue factor (TF). The expression of platelet endothelial cell adhesion molecule-1(CD31) protein was detected by immunohistochemistry. The colocalized expressions of proliferating cell nuclear antigen Ki67(Ki67) and CD31 in colonic tissues of rats were observed by immunofluorescence staining. The damage of colon mucosal barrier was observed by alcian blue-periodate Scheff (AB-PAS) staining. The expression of zonula occluden-1(ZO-1), Occludin and Claudin-1 proteins were detected by Western blot. The results showed that compared with the model group, the body weight of rats increased to varying degrees after treatment with PRA. Blood perfusion volume increased significantly. The inflammatory cell infiltration decreased significantly. The contents of TNF-α and IL-1β in serum and colon tissue decreased significantly, and the contents of IL-4 and IL-10 increased significantly, and the levels of serum PAF and TF were significantly decreased. The co-localized expressions of Ki67 and CD31 decreased, while the expression of ZO-1, Occludin and Claudin-1 protein significantly increased. PRA has a good therapeutic effect on UC rats, the mechanism of which may be related to the repair of intestinal mucosal mechanical barrier and the improvement of intestinal mucosal microcirculation disturbance by inhibiting colonic endothelial cell angiogenesis.