Treatment of skin allergic diseases remains a challenging research topic. To investigate the effect of Kushen recipe extractive (KS) gel on contact dermatitis (CD) of mouse. Allergic contact dermatitis (ACD) model of mouse was established. Immunohistochemical method (ICH) and flow cytometry method (FCM) were used to detect CD4+ and CD8+ T lymphocytes and explore the regulation effect of KS on the immune status of the organism. The expression status of eotaxin tissue was evaluated by real-time polymerase chain reaction (RT-PCR), ICH, and western blotting method. The survival rates of HaCaT cell and Fibroblasts affected by KS were detected by methyl thiazolyl tetrazolium (MTT) method. The inhibitory effect of KS on eotaxin produced by HaCaT cell and FBs induced by TNF-α and interleukin (IL)-4 were evaluated using RT-PCR and enzyme-linked immunosorbent assay methods. The inhibitory effect of KS on nuclear factor-κB (NF-κB) and Signal transducers and activators of transcription 6 (STAT6) activation induced by TNF-α and IL-4 was detected by electrophoretic mobility shift assay and western blotting methods. We confirmed that KS shows favorable therapeutic effect on CD, which can obviously inhibit eotaxin expression and Eosinophils recruitment in allergic skin of mouse, as well as regulate the immune status of the organism. Furthermore, KS and its main effective components can inhibit TNF-α and IL-4 induced upregulation of eotaxin via the two signal transduction pathways, NF-κB and STAT6. The great importance of traditional Chinese recipe KS is evidenced by its therapeutic effect and mechanism in ACD of mouse.