Background: Many studies showed a possible exacerbation of psoriasis after exposure to angiotensin receptor antagonists. Azilsartan is a competitive angiotensin II receptor antagonist and has anti-inflammatory effects in various inflammatory disorders. Objective: Investigate dose-dependent effects of topical Azilsartan on Imiquimod-induced psoriasis in mice. Methods: Forty-eight mice are allocated into six groups (8 mice per group). They all received Imiquimod for the induction of psoriasis (except Group I, a negative control group). Group II (Induction group) received petroleum gel for six days after induction with Imiquimod. The other groups (III, IV, V, and VI) were given Clobetasol propionate 0.05, 1% Azilsartan, 3% Azilsartan, and a combination of 3% Azilsartan and 0.05% Clobetasol propionate ointments, respectively once daily for six days after induction. Results: Azilsartan decreased psoriasis area severity index (PASI) score and attenuated the histological manifestations after induction. It significantly decreased the serum and tissue levels of the inflammatory biomarkers (TNF-α, IL-17, IL-23, and NF-Kβ), especially when used as an add-on therapy to Clobetasol. Conclusion: Topically-applied Azilsartan shows anti-psoriatic effects in Imiquimod-induced psoriasis in mice via anti-inflammatory and anti-proliferative activities.