Abstract: Although the use of aloe vera and coal tar in psoriasis treatment is well established, their mechanism of action is poorly understood. The aim of this study was to evaluate the therapeutic effectiveness of topical mixture of aloe vera extract and 1% coal tar (AMIX) in psoriasis and evaluate its antiproliferative, apoptotic and antiangiogenic effects as possible therapeutic mechanisms. AMIX was used in 279 patients with mild to moderate plaque psoriasis and PASI scores were recorded monthly. Skin biopsies from 30 patients before and after 3 months of therapy and 10 biopsies of normal skin were immunohistochemically stained using Ki67, Bcl-2 and CD34 antibodies as markers of cell proliferation, apoptosis and neoangiosis, respectively. Results: PASI scores decreased from 8.2±1.6 to 1.3±1.1 after 12 weeks of treatment (p<0.001) with complete clearance in 145 patients (~52%) without relapse during follow up period. Psoriatic skin showed higher expression of Ki67 in epidermal keratinocytes, Bcl-2 in basal keratinocytes and dermal inflammatory cells and CD34 in the dermal blood vessels compared to normal skin (p<0.001, p<0.01 and p<0.001, respectively). After treatment, Ki67, epidermal and dermal Bcl-2 and CD34 showed decreased expression (p<0.001, p<0.01, p>0.05 and p<0.001, respectively). These changes were positively correlated with the decrease in PASI scores. In conclusion, aloe vera and coal tar (AMIX) is an effective topical treatment of psoriasis without noticeable side effects. It causes inhibition of epidermal cell proliferation, neoangiogenesis and induction of apoptosis together with its immune modulatory effects.