Psoriasis is a chronic inflammatory skin disease, in which the key features are epidermis hyperplasia, hyperkeratinization, leading to low drug absorption. As an approach of transdermal drug delivery, the microneedle (MN) has received increasing attentions for its painless penetration and efficient administration. In this study, we fabricated polylactic acid polymer MNs with hot-press method and established a psoriasis-like skin inflammation model in ear and dorsal skin of mice by topical application of imiquimod (IMQ). The dynamometer and insertion test of MNs into parafilm and skin of mice were done, revealing that the MNs have sufficient mechanical properties to insert parafilm and skin of mice. The two methods (apply calcipotriol (CAL) directly and pre-treat with MNs before applying CAL) were used to treat psoriasis and observe the skin inflammation, including skin and epidermal thickening, spleen weight gain, inflammatory cell infiltration, and expression of inflammatory cytokines of TNF-alpha. Both methods have a therapeutic effect and the effect of the MN pretreatment group is better. In addition, there are statistical differences between the two groups (P < 0.05). These features indicated that the MNs may be promising in future clinical applications in improving the imiquimod-induced psoriasis like dermatitis.