BACKGROUND Previously, we demonstrated that the chlamydial protein pGP3 forms a stable complex with LL-37 to neutralize its proinflammatory activity during the pathogenesis of psoriasis. The middle domain of pGP3 (pGP3M) is critical for the binding and neutralization of LL-37. Here, we further examined the mechanism underlying pGP3-mediated inhibition of psoriasis progression and evaluated the inhibitory effect of pGP3M on the development of psoriasis-like skin lesions in mice. MATERIAL AND METHODS Stock solutions of pGP3M and pGP3 (100 μg/mL) were prepared using sterile ultrapure water and intramuscularly injected into the left leg of the imiquimod (IMQ)-induced psoriasis mouse model. The severity of skin lesions was evaluated based on the psoriasis area and severity index score and ear skin thickness. The skin biopsy and blood samples were collected on the 8th day for histological analysis and inflammatory cytokines detection. RESULTS Erythema, scaling, and thickening were observed on the dorsal skin and the right ear skin of IMQ-treated mice. Treatment with pGP3 and pGP3M alleviated the IMQ-induced erythema, inflammatory cell infiltration, and scaly plaques. Compared with IMQ-treated and PBS-treated mice, pGP3- and PGP3M-treated mice had less inflammatory cell infiltration in skin tissues and had significantly reduced IL-17A, IFN-γ, and IL-22 levels in serum. CONCLUSIONS The anti-psoriatic efficacy of exogenous pGP3M was similar to that of pGP3. This indicated that pGP3M attenuated the IMQ-induced inflammatory and psoriatic symptoms in mice by binding and inhibiting LL-37. Further research is needed to examine the toxicity of pGP3 and pGP3M before clinical trial evaluation.