French maritime pine bark (Pinus pinaster) extract (PBE), the registered trade name of which is Pycnogenol®, has been studied for its depigmenting action due to its antioxidant, anti-inflammatory, and anti-melanogenic activity. However, the mechanisms through which PBE are still not fully clear. Objective: Evaluate the impact of PBE on four in-vitro parameters closely associated with cutaneous pigmentation, including melanin synthesis, tyrosinase activity, endothelin-1 (ED1) and production of peroxisome proliferator-activated receptor ?, ????, and ? (PPAR ?, ????, and ?), by studying the modulation of action of ultraviolet radiation A (UVA)/ultraviolet radiation B (UVB), infrared-A (IR-A), visible light (VL), and association of UVA/UVB, IR-A, and VL (ASS). Methods: Human melanocytes were incubated in a dry extract solution of PBE, exposed to UVA/UVB, IR-A, VL, and ASS for subsequent quantification of melanin, ED1, and PPAR ?, ????, and ?. The effects of PBE on inhibition of tyrosinase activity were also performed by monophenolase activity assay. Results: UVA/UVB, IR-A, VL, and ASS radiation caused significant increases in the synthesis of melanin, ED1, and PPAR ?, ????, and ? when compared to baseline control. However, PBE significantly reduced the production of melanin, ED1, and PPAR ?, ????, and ?, as well as reducing about 66.5% of the tyrosinase activity. Conclusions: PBE reduces in vitro melanin production by downregulating tyrosinase and reducing pigmentation-related mediators, such as ED1 and PPAR ?, ????, and ?, therefore contributing to the inhibition of pathways associated with skin hyperpigmentation.