In this study, the effect of natural ceramide has been tested on primary cultures of cortical neurons. In order to study if the cortical neurons undergoing apoptosis, some markers such as the leakage rate of lactate dehydrogenase(LDH) and the MTT metabolic rate were assessed, also the morphological changes were observed by Giemsa staining. DNA ladders were determined by gel electrophoresis, as well as the cell ultrastructurales were observed under electronmicroscope. The results showed that 500 to 1000nM of ceramide could induce apoptosis of culture cortical neurons in dose-dependent and time-dependent way after 12 hrs of incubation. The ultrastructural changes are consistent with the changes observed by Giemsa staining or DNA ladders on gel electrophoresis.