Tyrosinase is a ubiquitous enzyme with diverse physiologic roles related to pigment production. Tyrosinase inhibition has been well studied for cosmetic, medicinal, and agricultural purposes. We simulated the docking of tyrosinase and D-(-)-arabinose and found a binding energy of -4.5 kcal/mol for theup-formof D-(-)-arabinose and -4.4 kcal/mol for thedown-form of D-(-)-arabinose. The results of molecular dynamics simulation suggested that D-(-)-arabinose interacts mostly with HIS85, HIS259, and HIS263, which are believed to be in the active site. Our kinetic study showed that D-(-)-arabinose is a reversible, mixed-type inhibitor of tyrosinase (α-value = 6.11 ± 0.98, K(i) = 0.21 ± 0.19 M). Measurements of intrinsic fluorescence showed that D-(-)-arabinose induced obvious tertiary changes to tyrosinase (binding constant K = 1.58 ± 0.02 M(-1), binding number n = 1.49 ± 0.06). This strategy of predicting tyrosinase inhibition based on specific interactions of aldehyde and hydroxyl groups with the enzyme may prove useful for screening potential tyrosinase inhibitors.