Melasma is considered the most common and visible pigmentary skin disorder that affects the face and can become a significant aesthetic discomfort. Exposure to UV light and drugs, as well as, genetic characteristics, chronic inflammation and hormonal influences are associated with the appearance of melasma, although the pathogenesis of this skin disorder is not fully understood. Studies have demonstrated a close relationship between melasma and increased expression of vascular markers, such as VEGF (vascular endothelium growth factor), and iNOS (inducible nitric oxide synthase) in the affected areas. VEGF has been implicated in the increased melanocyte activity, since the melanocytes exhibit functional receptors for VEGF, whereas iNOS causes release of NO and hence the stimulation of tyrosinase and transfer melanin to melanosome. The aim of this study was to evaluate the antiangiogenic and whitening effects of a depigmentation formulation (BLTX) using an in vitro model of human cell and skin culture. Human fibroblasts, keratinocytes or melanocytes were incubated with 3 non-cytotoxic concentrations of BLTX and subjected to oxidative stress by UV radiation or inflammatory stress with IL-1? for quantification of melanin, tyrosinase, endothelin-1, PAR-2, VEGF and iNOS. Cell supernatants and lysates were collected and mediators were quantified using colorimetric sandwich assay (ELISA). Fragments of human skin, from elective plastic surgery, were treated with BLTX and subjected to histological evaluation with hematoxylin/eosin associated with Fontana-Masson technique for melanin view. A parametric method, the one-way analysis of variance (Anova) followed by the Bonferroni test, was used to compare data among all groups. The results demonstrated that BLTX promotes a reduction in VEGF and iNOS protein synthesis in cultured dermal fibroblasts, indicating an antiangiogenic property. In relation to whitening effect, BLTX was able to reduce the production of melanin in both systems, melanocytes and human skin cultures. The depigmenting action was also revealed by decreasing the levels of endothelin-1, PAR-2, and activity of tyrosinase, when compared to cultures exposed to UV radiation. The results allow us to infer that BLTX presents an antiangiogenic effect indicating a role in the vascular component of melasma. Furthermore, the whitening property observed reinforces its use in the prevention and treatment of melasma.