Abstract: The present study was carried out to determine the effects of extracts of Citrus reticulata and its active ingredient hesperidin on the isolated tail melanophores of the Bufo melanostictus to find the mechanism of skin lightening at the cellular level. The tail melanophores of the tadpole B. melanostictus, were assayed using the mean melanophore size index and their responses were recorded in presence of various concentrations of the plant extract and its active ingredient along with specific antagonists and potentiator. Significant skin lightening activity of the extract of C. reticulata and hesperidin was observed on the tail melanophores of tadpole. The pigment cells responded by distinct aggregation leading to skin lightening, the effect was reversible, as re-immersion in physiological saline made the melanophores return to their normal intermediate state. These melanin aggregating effects were completely blocked by prazosin (alpha blocker) and were also found to be highly potentiated by reserpine. These studies suggest that the active ingredient of C. reticulata such as hesperidin can act as a sympathomimetic compound and induce aggregation of tail melanophore of tadpole Bufo melanostictus via induction of the alpha adrenoceptors. The present study opens new vistas for the use of C. reticulata and its active ingredient, hesperidin for its clinical application as a non toxic depigmenting compound for the treatment of hyperpigmentation.