Extrinsic aging is attributed to skin changes due to lifestyle and environmental insults. Cigarette smoke contains more than 4,000 toxic compounds including many polycyclic aromatic hydrocarbons, dioxins, and furans; all of then exert negative effects on the skin, contributing to extrinsic skin aging. Cigarette smoke induce the latent and non-functional form of transforming growth factor-?1 (TGF-?1); consequently, cellular responsiveness to TGB-?1 is blocked by this non-functional form, which results in decreased synthesis of extracellular matrix proteins, such as collagen. In this study, we evaluated the effects of honokiol – a natural biphenolic compound derived from the bark of magnolia trees, which presents anti-inflammatory, anti-oxidative, anti-tumour, and neuroprotective properties – through the quantification of collagen and TGF-?1 levels in human skin fragments exposed to cigarette smoke. Human skin fragments were incubated in culture medium and treated with honokiol (10µM and 20µM) and then exposed to cigarette smoke using a cigarette smoke chamber. Total collagen and TGF-?1 levels were measured in supernatants of skin fragments culture through ELISA method. Our results demonstrated that cigarette smoke promotes significant reduction (51.1%) in collagen synthesis and an increasing of TGF-?1 (2.1 fold), compared to control baseline group. Conversely, honokiol treatment prevented the substantial decline in the collagen synthesis in relation to the group exposed to cigarette smoke (8,62% and 29.4% at concentrations of 10µM and 20µM, respectively). Interestingly, incubation of the explants with honokiol plus cigarette smoke led to a further increase in the synthesis of TGF-?1 (86.5% and 19.1% at concentrations of 10µM and 20 µM, respectively). Honokiol appears to reverse the collagenolytic effects of smoking-induced TGF-?1 dysfunction.