Objective: To study the response of Cloudman S91 melanoma cells to the specific ingredients of some Chinese herbal medicine and discuss the mechanism of melanogenesis in response to different nature chemicals. Methods: Cloudman S91 melanoma cells were incubated for 72h at different concentrations of 6 nature chemicals, such as piperine, protocatechualdehyde, ginkagolide et al, which were purified from Chinese herbal medicines. Then the melanin content and tyrosinase activity were measured. The direct activity of mushroom tyrosinase in vitro was also detected by revised Matsuda's methods. Results: All of these 6 nature chemicals increased the cellular melanin content. Within them piperine, protocatechualdehyde and ginkagolide in their optimal concentrations stimulated the melanin generation even more effectively than 8-methoxypsoralen at 100 μmol/L concentration (P < 0.05). The piperine was most effective in the 0.5 mmol/L concentration. The tyrosinase activity tests showed that piperine stimulated the activity both within and without the cells. But ginkagolide showed the stimulating effect only within the cells, not out of the cells. To the contrary, protocatechualdehyde did out the cells, not within the cells. Conclusions: These nature chemicals, such as piperine, protocatechualdehyde and ginkagolide, can increase pigmentation of cloudman S91 melanoma. Protocatechualdehyde stimulates melanogenesis not by the induction of tyrosinase activity.