Background: T helper 17 (Th17) cells play an important role in the pathogenesis of psoriasis. Th17 differentiation and function are modulated by stromal interaction mol. 1 and/or store operated Ca2+ entry (STIM1/SOCE) pathway. Liangxue Huoxue Formula (LXHXF) is an effective traditional Chinese herbal formula used to treat psoriasis. But the specific mechanism of action is unclear. Here, we established a psoriasis animal model to evaluate the therapeutic effects of LXHXF and how it may regulate Th17 cell differentiation through STIM1/SOCE pathway. Methods: A psoriasis animal model was established using BALB/c male mice induced by imiquimod. Then, A course of 8-day intervention was conducted with methotrexate, STIM1 inhibitors, and LXHXF (high dose, medium dose, and low dose) in different groups. Skin lesions were recorded at the end of the intervention for pathol. evaluation. Immunohistochem. staining was conducted to assess the infiltration of Th17 cells. Moreover, we performed cytometric bead array (CBA) method and flow cytometry to determine serum inflammatory cytokines and the Th17 percentage in peripheral blood cells, resp. STIM1/SOCE pathway-related mRNA expression in skin lesions was also evaluated. Results: The model group presented typical psoriasiform manifestations, and the infiltration of Th17 cells in skin lesions increased significantly, compared to the control group (p < 0.05). In addition, the percentage of Th17 cells in peripheral blood and the level of inflammatory factors in serum, including interferon γ (IFN-γ), interleukin 17A (IL-17A), interleukin 21 (IL-21), and interleukin 22 (IL-22), increased in the model group compared to the control group (p < 0.05). mRNA expression level of STIM1 and calcium release-activated calcium modulator 1 (Orai1) in skin lesions increased after modeling (p < 0.05). LXHXF, Methotrexate, and STIM1 inhibitors intervention contributed to the reversion of the model-induced abnormalities to a certain extent (p < 0.05). LXHXF therapeutic effect suggested a dose-dependent effect. Conclusions: LXHXF may significantly improve the psoriasiform skin lesions in mice by imiquimod what improved Th17 infiltration and expression, inhibited inflammatory factors (IFN-γ, IL-17A, IL-21, and IL-22), and decreased Th17 percentage in peripheral blood. The mechanism may provide insights into the potential therapeutic strategy based on the STIM1/SOCE pathway.