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Objective To investigate the mechanism of capsaicin in treating active psoriasis vulgaris. Methods A total of 42 patients with active psoriasis vulgaris diagnosed by histology and clinical features were given either placebo or 0.025% capsaicin ointment four times daily for 30 days randomly by double-blind method. Vasoactive intestinal polypeptide receptor 1(VIPR1) gene translation in active psoriatic lesions before and after treatment with capsaicin ointment was detected by in situ hybridization. Results There was positive staining of VIPR1 gene in all the layers of psoriatic epidermis (95.5%) before the treatment with capsaicin ointment, but nearly no dyeing in epidermis (18.2%) after the treatment for 30 days. There was nearly no brown staining before and after treatment in control group. Conclusion VIPR1 gene translation in psoriatic epidermis is down-regulated after capsaicin treatment for 30 days.