Background and Objective: Due to the significant importance of the teeth in mastication, speech, and aesthetics, it is necessary to identify all involved genes in the tooth development. Therefore, this study aimed to evaluate the role of endothelin-1 and its A receptor in dental lamina in different stages of tooth development. Materials and Methods: This cross-sectional study included 33 fetal samples that were divided into three groups regarding gestational age. All samples were then stained by immunohistochemistry. Subsequently, the analysis was conducted in SPSS software (version 20) through the two-way ANOVA and Tukey's tests to examine the differences between the variables. A p-value less than 0.05 was considered statistically significant. Results: There was a significant difference between the gestational age and the expression level of endothelin-1 in dental lamina (P<0.001). In addition, a significant relationship was observed between age and anatomic area (P<0.001). There was also a significant difference between the gestational age and the expression level of endothelin-1 receptor (ETAR) in dental lamina (P<0.001). A significant association was found between gestational age and anatomic area (P<0.001). Conclusion: The expression levels of endothelin-1 and its receptor (ETAR) in each jaw were higher in anterior dental lamina, compared to posterior dental lamina. These results may confirm the role of endothelin-1 and its receptor in cell proliferation, differentiation of dental lamina, and calcium ion transport during tooth development.