Background: Psoriasis is a common inflammatory skin disorder. There has been considerable interest in herbal medicine as a treatment for psoriasis. In a previous study HESA-A, a marine-herbal drug, was found to be beneficial in the treatment of psoriasis vulgaris. The aim of this study was to assess the efficacy and tolerability of HESA-A in patients with psoriasis. Methods: Nineteen patients with a mean PASI score of 13.04±6.14 (min=3.90, max=27.70) were recruited to receive daily dosage of 30 mg/kg of HESA-A tablets for at least 4 weeks. The patients were followed every two weeks for determining PASI score changes and drug side effects until the end of the study. Result: At the end of the study, the mean PASI score of the patients reduced to 9.60±5.30 (min=0.90, max=19.1). PASI score reduced in 14 patients (73.7%) and increased in 5 patients (26.3%) during the study. Two patients achieved 75 to 100% improvement in PASI score and two achieved 50 to 75%. In 10 patients (52.6%), 1 to 50% improvement in the PASI score was detected. There was a statically significant correlation between the duration of treatment and PASI improvement. (P-value = 0.024) Conclusion: Although this drug was very safe and tolerable, our study did not find rapid and acceptable efficacy in the treatment of chronic plaque psoriasis as shown in a previous study. According to our findings, HESA-A was more effective when used for a prolonged time and in respect of the safety profile of HESA-A, we can use this drug as a maintenance or adjuvant therapy for chronic plaque psoriasis in longer terms.