〔Abstract〕 Objective To study the effect of crisaborole on imiquimod(IMQ)-induced psoriasis in mice. Methods Forty eight Balb/c mice were randomly divided into crisaborole group(7.5, 15, 30 mg/cm2), halometasone group(15 mg/cm2), model group and normal group. IMQ was applied to the back of mice to establish the psoriasis model. Psoriasis area and severity index(PASI) score was calculated, pathological changes, skin epidermal thickness and inflammatory cell infiltration in the dermis were observed by HE staining. The expressions of keratin(K)1, K10, K6, K16 and K17 in skin lesions were detected by Western blot and immunohistochemistry. The levels of cyclic adenosine monophosphate(cAMP), protein kinase A(PKA) and phospho-cAMP response element binding protein(p-CREB) were detected. Results Compared with the model group, the PASI score of the crisaborole group decreased, the expression levels of proliferative keratin(K6, K16 and K17) decreased(F=12.62、19.41、28.39,P<0.01), and the expression levels of differentiation keratin(K1 and K10) increased(F=27.95、9.64,P<0.01). Conclusion Crisaborole plays a therapeutic role in IMQ-induced psoriasis in mice by regulating the abnormal proliferation and differentiation of keratinocytes.