Objective: Qi deficiency and blood stasis syndrome is a common clinical pattern of chronic urticaria,However, there is relatively limited research on the establishment of standardized and scientifically accurate animal models for recurrent chronic urticaria with qi deficiency and blood stasis syndrome.. This study aimed to construct and evaluate an animal model of recurrent chronic urticaria with qi deficiency and blood stasis syndrome using drug intervention and re-challenge after rest.Methods: Thirty BALB/c mice were randomly divided into two groups: a control group (n=12) and a model group (n=18). The control group was fed a standard diet and housed under normal conditions. The model group was subjected to passive cutaneous sensitization, reserpine injection into the quadriceps femoris, and low-dose re-challenge after rest to establish the recurrent chronic urticaria model with qi deficiency and blood stasis syndrome. The model was evaluated based on general condition, body weight, scratching behavior, qi deficiency and blood stasis scores, tongue appearance, open-field test results, mechanical pain sensitivity, mechanical pain threshold, serum biomarkers, and histopathological examination.Results: After modeling, the model group exhibited significantly increased scratching behavior (P<0.01). Following the 6th and 7th immunizations, hematoxylin-eosin (HE) and toluidine blue staining revealed typical pathological features of chronic urticaria. The model mice displayed lethargy, reduced responsiveness to external stimuli, decreased activity, drowsiness, physical weakness, emaciation, dull fur, and dark-red ears, perianal regions, and claws. Compared with the control group, the model group showed reduced body weight (P<0.01), decreased average speed and total distance in the open-field test (P<0.01), elevated serum levels of adrenocortical hormones, nicotinic acetylcholine receptor α1, and adenosine diphosphate (P<0.01), reduced adenosine triphosphate (P<0.05), and a significantly lower mechanical pain threshold (P<0.01). Tongue image analysis indicated significantly decreased R, G, and B values (P<0.01), presenting as a "purplish tongue" or "dark-red tongue."Conclusion: The method combining passive cutaneous sensitization, reserpine injection into the quadriceps femoris, and low-dose re-challenge after rest can established an animal model of recurrent chronic urticaria with qi deficiency and blood stasis syndrome. Key evaluation indicators included scratching behavior, qi deficiency and blood stasis scores, tongue appearance, open-field test performance, mechanical pain sensitivity, mechanical pain threshold, serum biomarkers, and histopathological changes.