Abstract: OBJECTIVE To investigate the effect of melatonylvalpromide(Mtv) or melatonin(Mt) on calyculin A(CA) induced neurotoxicity. METHODS N2a cells were treated with DMSO, or 5 nmol·L^-1 CA, or 5 nmol·L^-1 CA and 50 μmol·L^-1 Mt, or 5 nmol·L^-1 CA and 50 μmol·L^-1 Mtv. Morphology changes were observed with inverted phase contrast microscope, index of apoptotic cell were measured with Hoechst33342 staining, MDA level of cell was analyzed with TBA assay, SOD activity was determined by assessing the inhibition of pyrogallol autooxidation, and CAT activity was analyzed with Colorimetry. RESULTS CA treatment resulted in the process of N2a cell retracting, thinning, and cell apoptosis, accompany with MDA level increasing, SOD and CAT activity decreasing. Both Mt and Mtv could partially antagonize the toxicity of CA, characterized by increasing processes length of cell, decreasing apoptotic cell population, and decreasing MDA level and increasing SOD activity. Moreover, the protective effect of Mtv was stronger than that of Mt. CONCLUSION Mtv has stronger protective effect than that of Mt on CA induced neurotoxicity.